COPI is a coatomer, a protein complex [1] that coats vesicles transporting proteins from the cis end of the Golgi complex back to the rough endoplasmic reticulum (ER), where they were originally synthesized, and between Golgi compartments. This type of transport[ clarification needed ] is retrograde transport, in contrast to the anterograde transport associated with the COPII protein. The name "COPI" refers to the specific coat protein complex that initiates the budding process on the cis-Golgi membrane. The coat consists of large protein subcomplexes that are made of seven different protein subunits, namely α, β, β', γ, δ, ε and ζ.
COPI | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
Symbol | COPI_C | ||||||||
Pfam | PF06957 | ||||||||
InterPro | IPR010714 | ||||||||
|
Coat protein, or COPI, is an ADP ribosylation factor (ARF)-dependent protein involved in membrane traffic. [2] COPI was first identified in retrograde traffic from the cis-Golgi to the rough endoplasmic reticulum (ER) [3] [4] and is the most extensively studied of ARF-dependent adaptors. COPI consists of seven subunits which compose the heteroheptameric protein complex.
The primary function of adaptors is the selection of cargo proteins for their incorporation into nascent carriers. Cargo containing the sorting motifs KKXX and KXKXX interact with COPI to form carriers which are transported from the cis-Golgi to the ER. [5] [6] [7] [8] [9] Current views suggest that ARFs are also involved in the selection of cargo for incorporation into carriers.
ADP ribosylation factor (ARF) is a GTPase involved in membrane traffic. There are 6 mammalian ARFs which are regulated by over 30 guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). ARF is post-translationally modified at the N-terminus by the addition of the fatty acid myristate.
ARF cycles between GTP and GDP-bound conformations. In the GTP-bound form, ARF conformation changes such that the myristate and hydrophobic N-terminal become more exposed and associate with the membrane. The interconversion between GTP and GDP bound states is mediated by ARF GEFs and ARF GAPs. At the membrane, ARF-GTP is hydrolyzed to ARF-GDP by ARF GAPs. Once in the GDP-bound conformation, ARF converts to a less hydrophobic conformation and dissociates from the membrane. Soluble ARF-GDP is converted back to ARF-GTP by GEFs.
Membrane deformation and carrier budding occurs following the collection of interactions described above. The carrier then buds off of the donor membrane, in the case of COPI this membrane is the cis-Golgi, and the carrier moves to the ER where it fuses with the acceptor membrane and its content is expelled.
On the surface of a vesicle COPI molecules form symmetric trimers ("triads"). The curved triad structure positions the Arf1 molecules and cargo binding sites proximal to the membrane. The β′- and α-COP subunits form an arch over the γζβδ-COP subcomplex, orienting their N-terminal domains such that the K(X)KXX cargo-motif binding sites are optimally positioned against the membrane. Thus β′- and α-COP do not form a cage or lattice as in COPII and clathrin coats as previously suggested; [12] instead, they are linked to one another via the γζβδ-COP subcomplexes, forming an interconnected assembly. [13] The triads are linked together with contacts of variable valence making up four different types of contacts. [14]
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 inside the cell before the vesicles are sent to their destination. It resides at the intersection of the secretory, lysosomal, and endocytic pathways. It is of particular importance in processing proteins for secretion, containing a set of glycosylation enzymes that attach various sugar monomers to proteins as the proteins move through the apparatus.
COPII is a coatomer, a type of vesicle coat protein that transports proteins from the rough endoplasmic reticulum to the Golgi apparatus. This process is termed anterograde transport, in contrast to the retrograde transport associated with the COPI protein. The name "COPII" refers to the specific coat protein complex that initiates the budding process. The coat consists of large protein subcomplexes that are made of four different protein subunits.
Brefeldin A is a lactone antiviral produced by the fungus Penicillium brefeldianum. Brefeldin A inhibits protein transport from the endoplasmic reticulum to the golgi complex indirectly by preventing association of COP-I coat to the Golgi membrane. Brefeldin A was initially isolated with hopes to become an antiviral drug but is now primarily used in research to study protein transport.
ADP ribosylation factors (ARFs) are members of the ARF family of GTP-binding proteins of the Ras superfamily. ARF family proteins are ubiquitous in eukaryotic cells, and six highly conserved members of the family have been identified in mammalian cells. Although ARFs are soluble, they generally associate with membranes because of N-terminus myristoylation. They function as regulators of vesicular traffic and actin remodelling.
Vesicular transport adaptor proteins are proteins involved in forming complexes that function in the trafficking of molecules from one subcellular location to another. These complexes concentrate the correct cargo molecules in vesicles that bud or extrude off of one organelle and travel to another location, where the cargo is delivered. While some of the details of how these adaptor proteins achieve their trafficking specificity has been worked out, there is still much to be learned.
The vesicular-tubular cluster (VTC), also referred to as the endoplasmic-reticulum–Golgi intermediate compartment (ERGIC), is an organelle in eukaryotic cells. This compartment mediates trafficking between the endoplasmic reticulum (ER) and Golgi complex, facilitating the sorting of cargo. The cluster was first identified in 1988 using an antibody to the protein that has since been named ERGIC-53.
The coatomer is a protein complex that coats membrane-bound transport vesicles. Two types of coatomers are known:
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 structural domains have been shown to exhibit guanine nucleotide exchange activity. Some GEFs can activate multiple GTPases while others are specific to a single GTPase.
ADP-ribosylation factor 1 is a protein that in humans is encoded by the ARF1 gene.
Coatomer subunit beta is a protein that in humans is encoded by the COPB1 gene.
General vesicular transport factor p115 is a protein that in humans is encoded by the USO1 gene.
Coatomer subunit alpha is a protein that in humans is encoded by the COPA gene.
ADP-ribosylation factor GTPase-activating protein 1 is an enzyme that in humans is encoded by the ARFGAP1 gene. Two transcript variants encoding different isoforms have been found for this gene.
Coatomer subunit epsilon is a protein that in humans is encoded by the COPE gene.
Coatomer subunit gamma-2 is a protein that in humans is encoded by the COPG2 gene.
Coatomer subunit gamma is a protein that in humans is encoded by the COPG gene. It is one of seven proteins in the COPI coatomer complex that coats vesicles as they bud from the Golgi complex.
Transmembrane emp24 domain-containing protein 2 is a protein that in humans is encoded by the TMED2 gene.
Clathrin adaptor proteins, also known as adaptins, are vesicular transport adaptor proteins associated with clathrin. These proteins are synthesized in the ribosomes, processed in the endoplasmic reticulum and transported from the Golgi apparatus to the trans-Golgi network, and from there via small carrier vesicles to their final destination compartment. The association between adaptins and clathrin are important for vesicular cargo selection and transporting. Clathrin coats contain both clathrin and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Therefore, adaptor proteins are responsible for the recruitment of cargo molecules into a growing clathrin-coated pits. The two major types of clathrin adaptor complexes are the heterotetrameric vesicular transport adaptor proteins (AP1-5), and the monomeric GGA adaptors. Adaptins are distantly related to the other main type of vesicular transport proteins, the coatomer subunits, sharing between 16% and 26% of their amino acid sequence.
The C-terminal domain ofBeta2-adaptin is a protein domain is involved in cell trafficking by aiding import and export of substances in and out of the cell.
Exomer is a heterotetrameric protein complex similar to COPI and other adaptins. It was first described in the yeast Saccharomyces cerevisiae. Exomer is a cargo adaptor important in transporting molecules from the Golgi apparatus toward the cell membrane. The vesicles it is found on are different from COPI vesicles in that they do not appear to have a "coat" or "scaffold" around them.