The cystatins are a family of

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

inhibitors which share a sequence

homology Homology may refer to: Sciences Biology *Homology (biology), any characteristic of biological organisms that is derived from a common ancestor * Sequence homology, biological homology between DNA, RNA, or protein sequences *Homologous chrom ...

and a common

tertiary structure Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may int ...

of an alpha helix lying on top of an anti-parallel beta sheet. The family is subdivided as described below. Cystatins show similarity to

fetuin Fetuins are blood proteins that are made in the liver and secreted into the bloodstream. They belong to a large group of binding proteins mediating the transport and availability of a wide variety of cargo substances in the bloodstream. Fetuin-A ...

kininogen Kininogens are precursor proteins for kinins, biologically active polypeptides involved in blood coagulation, vasodilation, smooth muscle contraction, inflammatory regulation, and the regulation of the cardiovascular and renal systems. Types o ...

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...

-rich

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

s and cystatin-related

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s. Cystatins mainly inhibit peptidase enzymes (another term for ''proteases'') belonging to peptidase families C1 (

papain Papain, also known as papaya proteinase I, is a cysteine protease () enzyme present in papaya (''Carica papaya'') and mountain papaya (''Vasconcellea cundinamarcensis''). It is the namesake member of the papain-like protease family. It has wide ...

family) and C13 ( legumain family). They are known to mis-fold to form

amyloid Amyloids are aggregates of proteins characterised by a Fibril, fibrillar morphology of 7–13 Nanometer, nm in diameter, a beta sheet (β-sheet) Secondary structure of proteins, secondary structure (known as cross-β) and ability to be Staining, ...

deposits and are implicated in several diseases.

Types

The cystatin family includes: * The Type 1 cystatins, which are intracellular and are present in the cytosol of many cell types, but can also appear in body fluids at significant concentrations. They are single-chain polypeptides of about 100 residues, which have neither

disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

s nor carbohydrate side-chains. Type 1 cystatins are also known as Stefins (after the Stefan Institute where they were first discovered ) * The Type 2 cystatins, which are mainly extracellular secreted polypeptides are largely acidic, contain four conserved cysteine

residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...

s known to form two

s, may be

glycosylated Glycosylation is the reaction in which a carbohydrate (or 'glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not alw ...

and/or

phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...

. They are synthesised with a 19- to 28-residue signal peptide. They are broadly distributed and found in most body fluids. * The Type 3 cystatins, which are multidomain proteins. The mammalian representatives of this group are the

kininogens Kininogens are precursor proteins for kinins, biologically active polypeptides involved in blood coagulation, vasodilation, smooth muscle contraction, inflammatory regulation, and the regulation of the cardiovascular and renal systems. Types o ...

. There are three different kininogens in mammals: H- (high-molecular-mass, ) and L- (low-molecular-mass) kininogen, which are found in a number of species, and T-kininogen, which is found only in rats. * Unclassified cystatins. These are cystatin-like proteins found in a range of organisms: plant phytocystatins, fetuin in mammals, insect cystatins, and a puff adder venom cystatin, which inhibits metalloproteases of the MEROPS peptidase family M12 (astacin/adamalysin). Also, a number of the cystatin-like proteins have been shown to be devoid of inhibitory activity.

Human cystatins

CST1 Cystatin-SN is a protein that in humans is encoded by the ''CST1'' gene. The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have l ...

CST2 Cystatin-SA is a protein that in humans is encoded by the ''CST2'' gene. The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have l ...

, CST3 (cystatin C, a marker of kidney function),

CST4 Cystatin-S is a protein that in humans is encoded by the ''CST4'' gene. The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lo ...

CST5 Cystatin-D is a protein that in humans is encoded by the ''CST5'' gene. The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have l ...

, CST6, CST7, CST8, CST9,

CST11 Cystatin-11 is a protein that in humans is encoded by the ''CST11'' gene. The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have ...

, CSTA (cystatin A), CSTB (cystatin B)

Plant cystatins

Plant cystatins have special characteristics which permit them to be classified in a special class called Phytocystatin. One is the presence of a N-terminal alpha-helix, present only in plant cystatins. Phytocystatins are involved in several process, including plant germination and defense. van Wyk et al. found some 19 different cystatins similar to oryzacystatin-I in the soybean along with related cysteine proteases.

Membrane permeability

Chicken cystatin quickly passed the membrane of MCF-10A neo

T cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...

and inhibited

cathepsin B Cathepsin B belongs to a family of lysosomal cysteine proteases known as the cysteine cathepsins and plays an important role in intracellular proteolysis. In humans, cathepsin B is encoded by the ''CTSB'' gene. Cathepsin B is upregulated in ce ...

when it was acylated with fatty acyl residues of 6-18 carbon atoms.

References

External links

* Protease inhibitors {{protein-stub