Variant surface glycoprotein (VSG) is a ~60kDa protein which densely packs the

cell surface The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extra ...

protozoa Protozoa (: protozoan or protozoon; alternative plural: protozoans) are a polyphyletic group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic debris. Historically ...

parasites Parasitism is a close relationship between species, where one organism, the parasite, lives (at least some of the time) on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The en ...

belonging to the genus ''

Trypanosoma ''Trypanosoma'' is a genus of kinetoplastids (class Trypanosomatidae), a monophyletic group of unicellular parasitic flagellate protozoa. Trypanosoma is part of the phylum Euglenozoa. The name is derived from the Ancient Greek ''trypano-'' (b ...

''. This genus is notable for their cell surface proteins. They were first isolated from ''

Trypanosoma brucei ''Trypanosoma brucei'' is a species of parasitic Kinetoplastida, kinetoplastid belonging to the genus ''Trypanosoma'' that is present in sub-Saharan Africa. Unlike other protozoan parasites that normally infect blood and tissue cells, it is excl ...

'' in 1975 by

George Cross The George Cross (GC) is the highest award bestowed by the British government for non-operational Courage, gallantry or gallantry not in the presence of an enemy. In the British honours system, the George Cross, since its introduction in 1940, ...

. VSG allows the trypanosomatid parasites to evade the mammalian host's immune system by extensive

antigenic variation Antigenic variation or antigenic alteration refers to the mechanism by which an Pathogen, infectious agent such as a protozoan, bacterium or virus alters the proteins or carbohydrates on its surface and thus avoids a host (biology), host immune r ...

. They form a 12–15 nm surface coat. VSG dimers make up ~90% of all cell surface protein and ~10% of total cell protein. For this reason, these proteins are highly immunogenic and an immune response raised against a specific VSG coat will rapidly kill trypanosomes expressing this variant. However, with each cell division there is a possibility that the progeny will switch expression to change the VSG that is being expressed. VSG has no prescribed

biochemical Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, ...

activity.

The parasite has a large cellular repertoire of antigenically distinct VSGs (~1500/2000 complete and partial (

pseudogene Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Pseudogenes can be formed from both protein-coding genes and non-coding genes. In the case of protein-coding genes, most pseudogenes arise as superfluous copies of fun ...

s)) located in

telomeric A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In most, if not ...

and subtelomeric arrays (on

megabase A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

chromosomes or minichromosomes). VSGs are expressed from a bloodstream expression site (BES, ES) in a polycistron by

RNA polymerase I RNA polymerase 1 (also known as Pol I) is, in higher eukaryotes, the polymerase that only transcribes ribosomal RNA (but not 5S rRNA, which is synthesized by RNA polymerase III), a type of RNA that accounts for over 50% of the total RNA synthesiz ...

(recruited to a ribosomal-type promoter) with other ES-associated genes (ESAGs), of which

transferrin receptor Transferrin receptor (TfR) is a carrier protein for transferrin. It is needed for the import of iron into cells and is regulated in response to intracellular iron concentration. It imports iron by internalizing the transferrin-iron complex throu ...

(Tfr: ESAG6, ESAG7) is one. Only one VSG gene is expressed at a time, as only one of the ~15 ES are active in a cell. VSG expression is 'switched' by

homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...

of a silent basic copy gene from an array (directed by homology) into the active telomerically located expression site. During this transition, trypanosomes simultaneously display both pre- and post-switch VSGs on their surface. This coat replacement process is critical for the survival of recently switched cells because initial VSGs remain targets for the escalating host Ab response. Mosaic VSG genes can be created by homologous recombination of a partial VSG gene from an array. This partial gene may replace any portion of the residing VSG gene, creating a new mosaic VSG. VSG half-life measurements suggest that initial VSGs may persist on the surface of genetically switched trypanosomes for several days. It remains unclear whether the regulation of VSG switching is purely stochastic or whether environmental stimuli affect switching frequency. The fact that switching occurs in vitro suggests that there is at least some host-independent, stochastic element to the process. The antigenic variation causes cyclical waves of parasitemia, which is one of the characteristics of human African trypanosomiasis. The cyclical process take 5–8 days. This occurs because a diverse range of coats expressed by the trypanosome population means that the immune system is always one step behind: it takes several days for an immune response against a given VSG to develop, giving the population time to diversify as individuals undergo further switching events. The repetition of this process prevents the extinction of the infecting trypanosome population, allowing chronic persistence of parasites in the host and enhancing opportunities for transmission.

In ''Trypanosoma brucei''

In ''Trypanosoma brucei'', the cell surface is covered by a dense coat of ~5 million VSG dimers, ~90% of all cell surface protein and ~10% of total cell protein. The properties of the VSG coat that enable immune evasion are: *Shielding – the dense nature of the VSG coat (VSG proteins pack shoulder-to-shoulder) prevents the immune system of the mammalian host from accessing the

plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

or any other parasitic invariant surface

epitopes An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although ep ...

(such as

ion channels Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ...

, transporters,

receptors Receptor may refer to: *Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds ...

etc.). The coat is uniform, made up of millions of copies of the same molecule; therefore, VSG is the only part of the trypanosome that the immune system can recognize. *Periodic

– the VSG coat undergoes frequent

stochastic Stochastic (; ) is the property of being well-described by a random probability distribution. ''Stochasticity'' and ''randomness'' are technically distinct concepts: the former refers to a modeling approach, while the latter describes phenomena; i ...

genetic modification—'switching'—allowing variants expressing a new VSG coat to escape the specific immune response raised against the previous coat. This antigenic variation creates cyclical waves of parasitemia characteristic of Human African Trypanosomiasis. *Antigen 'cleaning' and VSG recycling—VSG is efficiently recycled through the trypanosome flagellar pocket, allowing antibodies to be 'cleaned' from VSG before re-incorporation back into the cellular membrane. Importantly, VSGs recognized and bound by antibodies are selectively pushed toward the flagellar pocket at a quicker rate than unidentified VSG; in this scenario, the antibody acts as a 'sail', which quickens the process of VSG being brought to the area of recycling. The VSGs from ''T. brucei'' are attached to the plasma membrane via a covalent attachment to two glycosyl-phosphatidylinositol (GPI) anchors (one per

monomer A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization. Classification Chemis ...

), which directs its forward-trafficking from the ER to the flagellar pocket for incorporation into the membrane, as predicted by the GPI valence hypothesis. VSGs are replaced by an equally dense coat of procyclins when the parasite differentiates into the procyclic form in the

tsetse fly Tsetse ( , or ) (sometimes spelled tzetze; also known as tik-tik flies) are large, biting flies that inhabit much of tropical Africa. Tsetse flies include all the species in the genus ''Glossina'', which are placed in their own family, Gloss ...

midgut. There is a very fast inhibition of VSG gene transcription which occurs as soon as the temperature is lowered.

Expression

The source of VSG variability during infection is a large 'archive' of ''VSG'' genes present in the ''T. brucei''

genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...

. Some of these are full-length, intact

genes In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

; others are

pseudogenes Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Pseudogenes can be formed from both protein-coding genes and non-coding genes. In the case of protein-coding genes, most pseudogenes arise as superfluous copies of fun ...

(typically with frameshift mutations, premature stop codons, or fragmentation). Expression of an antigenically different VSG can occur by simply switching to a different full-length ''VSG'' gene by Expression Site switching (switching which ES is active). In addition, chimeric or 'mosaic' ''VSG'' genes can be generated by combining segments from more than one silent ''VSG'' gene. The formation of mosaic ''VSG''s allows the (partial) expression of pseudogene ''VSG''s, which can constitute the major portion of the ''VSG'' archive, and can contribute directly to antigenic variation, vastly increasing the trypanosome's capacity for immune evasion and posing a major problem for

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...

development. ''VSG'' genes can be kept silent and switched on at any given time. The expressed ''VSG'' is always located in an Expression Site (ES), which are specialised expression loci found at the

telomeres A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In most, if not ...

of some of the large and intermediate chromosomes. Each ES is a polycistronic unit, containing a number of Expression Site-Associated Genes (ESAGs) all expressed along with the active VSG. While multiple ES exist, only a single one is ever active at one time. A number of mechanisms appear to be involved in this process, but the exact nature of the silencing is still unclear. The expressed VSG can be switched either by activating a different expression site (and thus changing to express the ''VSG'' in that site), or by changing the ''VSG'' gene in the active site to a different variant. The genome contains many copies of VSG genes, both on minichromosomes and in repeated sections in the interior of the chromosomes. These are generally silent, typically with omitted sections or premature stop codons, but are important in the evolution of new VSG genes. It is estimated up to 10% of the ''T.brucei'' genome may be made up of VSG genes or

. Any of these genes can be moved into the active site by recombination for expression. Again, the exact mechanisms that control this are unclear, but the process seems to rely on

DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...

machinery and a process of

. The bloodstream expression site (BES), or telomeric expression site, is used for exchanging variant surface glycoproteins when in host's blood stream to escape the

complement system The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inf ...

. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of ''expression site associated genes'' (ESAGs). There is a collection of an estimated 20-30 sites, each being active at a time. Active VSG expression sites are depleted of

nucleosome A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone, histone proteins and resembles thread wrapped around a bobbin, spool. The nucleosome ...

s. The gene repertoires in ''T. brucei'' have diverged to become strain-specific. The variant surface glycoprotein genes of ''T. brucei'' have been classified into two groups depending upon whether or not duplication of the genes is observed when they are expressed. Mechanisms of VSG switching2

Secretory trafficking

''Trypanosoma'' have a simple, polarized membrane transport system consisting of a single ER,

lysosome A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...

, and

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

. VSG is first transcribed as a polycistron and then undergoes trypanosomatid-specific poly-adenylation and

trans-splicing ''Trans''-splicing is a special form of RNA processing where exons from two different primary RNA transcripts are joined end to end and ligated. It is usually found in eukaryotes and mediated by the spliceosome, although some bacteria and archa ...

directed by

polypyrimidine tract {{Short description, A pyrimidine-rich sequence involved in pre-messenger RNA maturation The polypyrimidine tract is a region of pre-messenger RNA (mRNA) that promotes the assembly of the spliceosome, the protein complex specialized for carrying ...

s. Because there is no transcriptional control, the VSG 3'UTR is important for its RNA stability (most importantly, the 8mer and 14mer). VSG is then transcribed on membrane-bound

polysome A polyribosome (or polysome or ergosome) is a group of ribosomes bound to an mRNA molecule like “beads” on a “thread”. It consists of a complex of an mRNA molecule and two or more ribosomes that act to translate mRNA instructions into p ...

s, and the appearance of the N-terminal signal sequence directs VSG to the ER. VSG is thereby co-translationally transported into the ER lumen, rapidly N-glycosylated (on asn-x-ser/thr sites) and GPI anchored at the ω site by a

transamination Transamination is a chemical reaction that transfers an amino group to a ketoacid to form new amino acids.This pathway is responsible for the deamination of most amino acids. This is one of the major degradation pathways which convert essential a ...

reaction (removing of the C-term hydrophobic 17 or 23 aa GPI anchoring sequence). The ω site is always Ser (usually in 17 aa signal sequence peptides), Asp (usually in 23 aa signal sequence peptides), or Asn. Also, the number of

N-glycosylation ''N''-linked glycosylation is the attachment of an oligosaccharide, a carbohydrate consisting of several sugar molecules, sometimes also referred to as glycan, to a nitrogen atom (the amide nitrogen of an asparagine (Asn) residue of a protein), i ...

sites per VSG may vary (usually 1-3 N-glycans). VSG MITat.1.5 is glycosylated at all three potential N-glycosylation sites. VSG then undergoes the

calreticulin Calreticulin also known as calregulin, CRP55, CaBP3, calsequestrin-like protein, and endoplasmic reticulum resident protein 60 (ERp60) is a protein that in humans is encoded by the ''CALR'' gene. Calreticulin is a multifunctional soluble prot ...

calnexin Calnexin (CNX) is a 67kDa integral protein (that appears variously as a 90kDa, 80kDa, or 75kDa band on western blotting depending on the source of the antibody) of the endoplasmic reticulum (ER). It consists of a large (50 kDa) N-terminal calciu ...

folding cycle (calnexin is absent in ''Trypanosoma brucei''), where it is transiently monoglucosylated and deglucosylated, and interacts with various ER chaperone proteins, such as BiP, in order to fold correctly. VSG efficiently folds and dimerizes (suggesting intrinsically favorable folding) and is transported through the Golgi to the flagellar pocket for incorporation into the cell membrane. Importantly, following incorporation into the cellular membrane, VSG may later be recycled through the flagellar pocket and sorted back to the cell surface. VSG is not turned over by lysosomal or proteasomal canonical degradation pathways, but is instead lost from the cell by specific cleavage of its GPI anchor by GPI-specific PLC.

Structure

VSG genes are hugely variable at the

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is cal ...

(primary) level, but variants are thought to have strongly conserved

structural A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

(tertiary) features, based on two determined 3-dimensional structures and conservation of 2-dimensional sequence motifs (descending and ascending alpha-helices that make up the dimerization interface), allowing them to perform a similar shielding function. VSGs are made up of

N terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

domain A domain is a geographic area controlled by a single person or organization. Domain may also refer to: Law and human geography * Demesne, in English common law and other Medieval European contexts, lands directly managed by their holder rather ...

of around 300–350

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

with low sequence homology (13–30% identity), and a more conserved

C terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

domain of ~100 amino acids. N-terminal domains are grouped into classes A-C depending on their cysteine patterns. C-term domains are grouped by sequence homology into classes I-III, with apparently no restriction on which N-term classes they can pair with to form a full VSG. To dimerize, VSG N-terminal domains form a bundle of four

alpha helices An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...

directed by hydrophobic interactions, around which hang smaller structural features (five smaller helices and three beta-sheets). VSG is anchored to the cell membrane via a glycophosphatidylinositol (GPI) anchor—a noncovalent linkage from the C-terminus which directs its forward trafficking from the ER to the membrane. This GPI anchor is specifically cleaved by GPI Phospholipase C, cleaving the membrane-form VSG, and allowing VSG protein and portion of the GPI anchor to be lost into the extracellular milieu as soluble VSG (sVSG, which is can be recognized as Cross-Reacting Determinant, or CRD), while retaining the two 1,2-dimyristolglycerol chains in the membrane. PDB 1vsg EBI

Antigenic variation

VSG is highly

immunogenic Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injectio ...

, and an

immune response An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...

raised against a specific VSG coat will rapidly kill trypanosomes expressing this variant.

Antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

-mediated trypanosome killing can also be observed ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' by a complement-mediated

lysis Lysis ( ; from Greek 'loosening') is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ...

assay An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity ...

. However, with each

cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...

there is a possibility that one or both of the progeny will switch expression to change the VSG that is being expressed. The frequency of VSG switching has been measured to be approximately 0.1% per division, though switching rates do differ in culture vs. ''in vivo''. As ''T. brucei'' populations can peak at a size of 10¹¹ within a host this rapid rate of switching ensures that the parasite population is constantly diverse. A diverse range of coats expressed by the trypanosome population means that the immune system is always one step behind: it takes several days for an immune response against a given VSG to develop, giving the population time to diversify as individuals undergo further switching events. Reiteration of this process prevents extinction of the infecting trypanosome population, allowing chronic persistence of parasites in the host, enhancing opportunities for transmission. The clinical effect of this cycle is successive 'waves' of parasitaemia (trypanosomes in the blood).

In other trypanosomes

Variable surface glycoproteins are also found in other ''

'' species. In ''

Trypanosoma equiperdum ''Τrypanosoma equiperdum'' is a species of kinetoplastid parasites that causes covering sickness in horses and other animals in the family Equidae. ''T. equiperdum'' is the only known trypanosome that is not spread by an insect vector. There ha ...

'', a parasite causing the

covering sickness Covering sickness, or dourine (French, from the Arabic ''darina'', meaning mangy (said of a female camel), feminine of ''darin'', meaning dirty), is a disease of horses and other members of the family Equidae. The disease is caused by '' Trypanoso ...

in horses, these proteins allow the parasite to efficiently evade the host animal's immune system. These VSGs allow the organism to constantly manipulate and change the surface structure of its proteins, which means it is constantly being presented to the immune system as a new foreign organism and this prevents the body from mounting a large enough immune response to eradicate the disease. In this sense, ''Trypanosoma equiperdum'' is a very efficient organism; it may infect fewer species than other diseases, but it infects and survives very efficiently within its specified hosts. The VSG proteins in ''T. equiperdum'' are also

phosphorylated In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...

. A VSG gene from ''

Trypanosoma evansi ''Trypanosoma evansi'' is a parasitic species of excavate trypanosome in the genus ''Trypanosoma'' that is one cause of surra in animals. Discovered by Griffith Evans in 1880 at Dera Ismail Khan (British India), it is the first known trypanoso ...

'', a parasite that causes a form of

surra Surra (from the Marathi language, Marathi ''sūra'', meaning the sound of heavy breathing through nostrils, of imitative origin) is a disease of vertebrate animals. The disease is caused by protozoan trypanosomes, specifically ''Trypanosoma e ...

in animals, has been cloned in ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

''. The expressed protein is immunoreactive with all the sera combinations. The animals immunized with whole cell lysate or recombinant protein show similar antibody reactions in

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...

(enzyme-linked immunosorbent assay) and CATT ( card agglutination test for trypanosomiasis). The variable surface glycoprotein RoTat 1.2 PCR can be used as a specific diagnostic tool for the detection of ''T. evansi'' infections. The smallest VSG protein (40 kDa in size) to date (1996) has been found in '' Trypanosoma vivax'', which bears little carbohydrate. In '' Trypanosoma congolense'', ''in vitro'' analyses of the incorporated sugars after hydrolysis of the glycoprotein showed that

glucosamine Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of two polysaccharides, chitosan and chitin. Glucosamine is one of the mo ...

and

mannose Mannose is a sugar with the formula , which sometimes is abbreviated Man. It is one of the monomers of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylatio ...

are utilized in the biosynthesis of the carbohydrate moiety directly whereas galactose was converted possibly to other intermediates before being incorporated into the antigen. The unglycosylated VSG with a molecular weight of 47 kDa had completely lost its size heterogeneity.

References

External links

* {{MeSH name, Variant Surface Glycoproteins, Trypanosoma
www.icp.ucl.ac.be
Kinetoplastid proteins Glycoproteins Parasitic excavates