The coatomer is a
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 ...
complex that coats membrane-bound
transport vesicles. Two types of coatomers are known:
*
COPI
COPI is a coatomer, a protein complex that coats vesicles transporting proteins from the ''cis'' end of the Golgi complex
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most ...
(retrograde transport from
trans-Golgi network
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...
to
cis-Golgi network and
endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
)
*
COPII
The Coat Protein Complex II, or COPII, is a group of proteins that facilitate the formation of vesicles to transport proteins from the endoplasmic reticulum to the Golgi apparatus or endoplasmic-reticulum–Golgi intermediate compartment. This ...
(anterograde transport from ER to the cis-Golgi)
Coatomers are functionally analogous and evolutionarily homologous to
clathrin adaptor proteins, also known as adaptins, which regulate
endocytosis
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
from the
plasma membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
and transport from the trans-Golgi network to
lysosomes
A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prote ...
.
Structure
The coatomer protein complex is made up of seven nonidentical
protein subunit
In structural biology, a protein subunit is a polypeptide chain or single protein molecule that assembles (or "''coassembles''") with others to form a protein complex.
Large assemblies of proteins such as viruses often use a small number of ty ...
s.
These seven nonidentical protein subunits are part of two protein subcomplexes.
The first subcomplex consists of Ret1(α-COP), Sec27(β’-COP), and Sec 28(ε-COP).
The second subcomplex consists of Sec26 (β-COP), Sec21 (γ-COP), Ret2(δ-COP), and Ret3 (ζ-COP).
COP I
COPI is a coatomer that coats the
vesicles
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane
* Synaptic vesicle
; In human embryology
* Vesicle (embryology), bulge-like features o ...
transporting proteins from the
Golgi complex
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles insi ...
to the ER.
This pathway is referred to as retrograde transport. Before the COP I protein can coat vesicles on the Golgi membrane, it must interact with a small
GTPase
GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a pro ...
called
ARF1
ADP-ribosylation factor 1 is a protein that in humans is encoded by the ''ARF1'' gene.
Function
ADP-ribosylation factor 1 (ARF1) is a member of the human ARF gene family. The family members encode small guanine nucleotide-binding proteins that ...
(ADP ribosylation factor).
ARF1 that is bound to
GDP
Gross domestic product (GDP) is a monetary measure of the market value of all the final goods and services produced and sold (not resold) in a specific time period by countries. Due to its complex and subjective nature this measure is ofte ...
interacts with the golgi complex membrane.
Next,
guanine nucleotide exchange factor
Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structu ...
s (GEFs) in the golgi complex membrane exchange the GDP bound to ARF1 for
GTP.
This activates ARF1, allowing it to insert an amphipathic
alpha helix
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...
into the
lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
of the Golgi complex.
Next, the ARF1 protein recruits COP1 to the golgi complex membrane by interacting with β-COP and γ-COP.
Once the vesicle is coated, it begins to travel to the ER. Before the vesicle can fuse with the ER membrane, the coats surrounding the vesicle must dissociate. ARF-GAP1 is responsible for deactivating the ARF1 protein by activating the GTPase.
When ARF1 switches to its GDP- bound conformation, it causes the COP1 coat to destabilize.
The COP1 proteins recognize the proper cargo by interacting with sorting signals on the cytoplasmic domains of the protein.
The most common sorting signals include the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
sequence KKXX or
KDEL.
KKXX signals are associated with
transmembrane
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
ER domains and KDEL signals are associated with proteins in the ER
lumen.
COP1 coated vesicles also contain
p24 proteins that assist with cargo sorting.
COP II
COP II is a coatomer that coats the vesicles transporting proteins from the ER to the golgi complex.
This pathway is referred to as anterograde transport.
The first step in the COP II pathway is the recruitment of a small GTPase named
Sar1 to the ER membrane.
Once Sar1 interacts with the ER membrane, a membrane protein called Sec12 acts a
guanine nucleotide exchange factor
Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structu ...
and substitutes GTP for GDP on Sar1.
This activates the Sar1 protein, causing its
amphipathic
An amphiphile (from the Greek αμφις amphis, both, and φιλíα philia, love, friendship), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'') properties. Such a compoun ...
alpha helix to bind to the ER membrane.
Membrane bound Sar1 attracts the Sec23-Sec24 protein
heterodimer
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...
to the ER membrane. Sar1 directly binds to
Sec23 while
Sec24 directly binds to the cargo receptor located on the ER membrane.
The Sar1-GTP and Sec23-24 complex recruits another protein complex called
Sec13/
Sec31
SEC31 is a protein which in yeast promotes the formation of COPII transport vesicles from the Endoplasmic Reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the select ...
. This complex polymerizes to form the outer layer of the coat.
COP II vesicles must shed their coat before they can fuse with the cis-Golgi membrane. This occurs when the GTP on Sar1 is hydrolyzed by the GTPase activating protein.
Activation of the GTPase also reverses the interaction between Sar1 and the Sec23-Sec24 protein dimer.
COP II vesicles select the proper cargo by directly interacting with ER export signals that are present in transmembrane ER proteins.
There are several classes of ER export signals that have been identified in various organisms. The involvement of so many different ER export signals means that there are multiple binding sites for the export signals.
Diseases associated with defects in COP
Newly made secretory proteins must pass through the ER and the golgi complex before they can leave the cell. Problems with COP II early secretory pathways can lead to a disease called
Congenital Dyserythropoietic Anemia type II
Congenital dyserythropoietic anemia type II (CDA II), or hereditary erythroblastic multinuclearity with positive acidified serum lysis test (HEMPAS) is a rare genetic anemia in humans characterized by hereditary erythroblastic multinuclearity with ...
.
This is an
autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
disorder that results from the mutation of a gene called
Sec23B.
This
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
plays an important role in regulating the transport of proteins within cells.
Symptoms for Congenital Dyserythropoietic Anemia type II include
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
,
jaundice
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
, low
reticulocyte
Reticulocytes are immature red blood cells (RBCs). In the process of erythropoiesis (red blood cell formation), reticulocytes develop and mature in the bone marrow and then circulatory system, circulate for about a day in the blood stream before ...
count,
splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulating ...
, and
hemochromatosis
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosi ...
.
Congenital Dyserythropoeitic Anemia Type II is normally diagnosed during adolescence or early adulthood.
Congenital Dyserythropoetic Anemia Type II is a very rare disease with only a few hundred cases worldwide.
Treatment for the disease involves blood transfusions, iron therapy, and the removal of the
spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . .
Another disease associated with deficiencies in the COP II pathway is combined
factor V
Factor V (pronounced factor five) is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor. Deficienc ...
and
factor VIII
Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the ''F8'' gene. Defects in this gene result in hemophilia A, a recessive X-linked coagulation disorder. ...
deficiency.
In this disease, the person produces Factor V and VIII but they can not transport factor V or VIII into the bloodstream.
This is an autosomal recessive disorder that leads to bleeding symptoms,
epistaxis
A nosebleed, also known as epistaxis, is bleeding from the nose. Blood can flow down into the stomach, and cause nausea and vomiting. In more severe cases, blood may come out of both nostrils. Rarely, bleeding may be so significant that low bloo ...
,
menorrhagia
Heavy menstrual bleeding (HMB), previously known as menorrhagia or hypermenorrhea, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding
Abnormal uterine bleeding (AUB), also known as (AVB) or as atypical ...
, and excessive bleeding after trauma.
The disease can be diagnosed after screening tests are analyzed by a specialized healthcare provider.
The mutation of the
MCFD2 gene is what causes combined factor V and VIII deficiency.
Treatment for the disease includes administrating frozen plasma and
desmopressin
Desmopressin, sold under the trade name DDAVP among others, is a medication used to treat diabetes insipidus, bedwetting, hemophilia A, von Willebrand disease, and high blood urea levels. In hemophilia A and von Willebrand disease, it should on ...
to the patient.
References
{{Vesicular transport proteins
Peripheral membrane proteins