COPI

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Electron micrograph of in vitro-formed COPI-coated vesicles. Average vesicle diameter at the membrane level is 60 nm. COPI coated vesicles.png
Electron micrograph of in vitro–formed COPI-coated vesicles. Average vesicle diameter at the membrane level is 60 nm.

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.

Contents

COPI
Identifiers
SymbolCOPI_C
Pfam PF06957
InterPro IPR010714
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Coat proteins

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.

Budding process

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.

  1. Luminal proteins: Proteins found in the lumen of the Golgi complex that need to be transported to the lumen of the ER contain the signal peptide KDEL. [10] This sequence is recognized by a membrane-bound KDEL receptor. In yeast, this is ERD2P and in mammals it is KDELR. This receptor then binds to an ARF-GEF, a class of guanine nucleotide exchange factors. This protein in turn binds to the ARF. This interaction causes ARF to exchange its bound GDP for GTP. Once this exchange is made ARF binds to the cytosolic side of the cis-Golgi membrane and inserts the myristoylated N-terminal amphipathic alpha-helix into the membrane. [11]
  2. Membrane proteins: Transmembrane proteins which reside in the ER contain sorting signals in their cytosolic tails which direct the protein to exit the Golgi and return to the ER. These sorting signals, or motifs, typically contain the amino acid sequence KKXX or KXKXX, which interact with COPI subunits α-COP and β'-COP. [10] [9] The order in which adaptor proteins associate with cargo, or adaptor proteins associate with ARFs is unclear, however, in order to form a mature transport carrier coat protein, adaptor, cargo, and ARF must all associate.

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.

Structure

The COPI triad. Color scheme: membrane - gray; Arf1 - pink; gamma-COP - light green; beta-COP, dark green; zeta-COP - yellow; delta-COP - orange; betaprime-COP - light blue; alpha-COP - dark blue The structure of the COPI triad.png
The COPI triad. Color scheme: membrane - gray; Arf1 - pink; gamma-COP - light green; beta-COP, dark green; zeta-COP - yellow; delta-COP - orange; betaprime-COP - light blue; alpha-COP - dark blue

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]

See also

Related Research Articles

<span class="mw-page-title-main">Golgi apparatus</span> Cell organelle that packages proteins for export

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.

A cisterna is a flattened membrane vesicle found in the endoplasmic reticulum and Golgi apparatus. Cisternae are an integral part of the packaging and modification processes of proteins occurring in the Golgi.

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 process is termed anterograde transport, in contrast to the retrograde transport associated with the COPI complex. COPII is assembled in two parts: first an inner layer of Sar1, Sec23, and Sec24 forms; then the inner coat is surrounded by an outer lattice of Sec13 and Sec31.

<span class="mw-page-title-main">Brefeldin A</span> Chemical compound

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.

<span class="mw-page-title-main">ADP ribosylation factor</span> Group of proteins

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.

<span class="mw-page-title-main">Vesicular transport adaptor protein</span>

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.

<span class="mw-page-title-main">ERGIC</span> Transport organelle in eukaroytes

The endoplasmic-reticulum–Golgi intermediate compartment (ERGIC) is an organelle in eukaryotic cells. This compartment mediates transport 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. It is also referred to as the vesicular-tubular cluster (VTC) or, originally, tubulo-vesicular compartment.

The coatomer is a protein complex that coats membrane-bound transport vesicles. Two types of coatomers are known:

<span class="mw-page-title-main">Guanine nucleotide exchange factor</span> Proteins which remove GDP from GTPases

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.

<span class="mw-page-title-main">ARF1</span> Protein-coding gene in the species Homo sapiens

ADP-ribosylation factor 1 is a protein that in humans is encoded by the ARF1 gene.

<span class="mw-page-title-main">COPB1</span> Protein-coding gene in humans

Coatomer subunit beta is a protein that in humans is encoded by the COPB1 gene.

<span class="mw-page-title-main">COPA (gene)</span> Protein-coding gene in humans

Coatomer subunit alpha is a protein that in humans is encoded by the COPA gene.

<span class="mw-page-title-main">COPE (gene)</span> Protein-coding gene in the species Homo sapiens

Coatomer subunit epsilon is a protein that in humans is encoded by the COPE gene.

<span class="mw-page-title-main">COPB2</span> Protein-coding gene in humans

Coatomer subunit beta is a protein that is encoded by the COPB2 gene in humans.

<span class="mw-page-title-main">COPG</span> Protein-coding gene in humans

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.

KDEL is a target peptide sequence in mammals and plants located on the C-terminal end of the amino acid structure of a protein. The KDEL sequence prevents a protein from being secreted from the endoplasmic reticulum (ER) and facilitates its return if it is accidentally exported.

Clathrin adaptor proteins, also known as adaptins, are vesicular transport adaptor proteins associated with clathrin. 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.

<span class="mw-page-title-main">Beta2-adaptin C-terminal domain</span> Protein family

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.

Halperin-Birk syndrome (HLBKS) is a rare autosomal recessive neurodevelopmental disorder caused by a null mutation in the SEC31A gene. Signs and symptoms include intrauterine growth retardation, marked developmental delay, spastic quadriplegia with profound contractures, dysmorphism, and optic nerve atrophy with no eye fixation. Brain MRI demonstrated microcephaly and agenesis of the corpus callosum.

References

  1. ↑ Coat+Protein+Complex+I at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  2. ↑ Serafini T, Orci L, Amherdt M, Brunner M, Kahn RA, Rothman JE (1991). "ADP-ribosylation factor is a subunit of the coat of Golgi-derived COP-coated vesicles: a novel role for a GTP-binding protein". Cell. 67 (2): 239–53. doi: 10.1016/0092-8674(91)90176-Y . PMID   1680566. S2CID   9766090.
  3. ↑ Schekman R, Orci L (1996). "Coat proteins and vesicle budding". Science. 271 (5255): 1526–1533. Bibcode:1996Sci...271.1526S. doi:10.1126/science.271.5255.1526. PMID   8599108. S2CID   30752342.
  4. ↑ Cosson P, Letourneur F (1997). "Coatomer (COPI)-coated vesicles: role in intracellular transport and protein sorting". Curr Opin Cell Biol. 9 (4): 484–7. doi:10.1016/S0955-0674(97)80023-3. PMID   9261053.
  5. ↑ Letourneur F, Gaynor EC, Hennecke S, Démollière C, Duden R, Emr SD, et al. (1994). "Coatomer is essential for retrieval of dilysine-tagged proteins to the endoplasmic reticulum". Cell. 79 (7): 1199–207. doi:10.1016/0092-8674(94)90011-6. PMID   8001155. S2CID   9684135.
  6. ↑ Sohn K, Orci L, Ravazzola M, Amherdt M, Bremser M, Lottspeich F, et al. (1996). "A major transmembrane protein of Golgi-derived COPI-coated vesicles involved in coatomer binding". J Cell Biol. 135 (5): 1239–48. doi:10.1083/jcb.135.5.1239. PMC   2121093 . PMID   8947548.
  7. ↑ Sönnichsen B, Watson R, Clausen H, Misteli T, Warren G (1996). "Sorting by COP I-coated vesicles under interphase and mitotic conditions". J Cell Biol. 134 (6): 1411–25. doi:10.1083/jcb.134.6.1411. PMC   2120996 . PMID   8830771.
  8. ↑ Orci L, Stamnes M, Ravazzola M, Amherdt M, Perrelet A, Söllner TH, et al. (1997). "Bidirectional transport by distinct populations of COPI-coated vesicles". Cell. 90 (2): 335–49. doi: 10.1016/S0092-8674(00)80341-4 . PMID   9244307. S2CID   18246842.
  9. 1 2 Ma, Wenfu; Goldberg, Jonathan (2013-04-03). "Rules for the recognition of dilysine retrieval motifs by coatomer". The EMBO Journal. 32 (7): 926–937. doi:10.1038/emboj.2013.41. ISSN   1460-2075. PMC   3616288 . PMID   23481256.
  10. 1 2 Mariano Stornaiuolo; Lavinia V. Lotti; Nica Borgese; Maria-Rosaria Torrisi; Giovanna Mottola; Gianluca Martire & Stefano Bonatti (March 2003). "KDEL and KKXX Retrieval Signals Appended to the Same Reporter Protein Determine Different Trafficking between Endoplasmic Reticulum, Intermediate Compartment, and Golgi Complex". Molecular Biology of the Cell. 14 (3): 889–902. doi:10.1091/mbc.E02-08-0468. PMC   151567 . PMID   12631711.
  11. ↑ Goldberg, J. (1998-10-16). "Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP-myristoyl switching". Cell. 95 (2): 237–248. doi: 10.1016/s0092-8674(00)81754-7 . ISSN   0092-8674. PMID   9790530. S2CID   15759753.
  12. ↑ Lee, Changwook; Goldberg, Jonathan (2010-07-09). "Structure of coatomer cage proteins and the relationship among COPI, COPII, and clathrin vesicle coats". Cell. 142 (1): 123–132. doi:10.1016/j.cell.2010.05.030. ISSN   1097-4172. PMC   2943847 . PMID   20579721.
  13. ↑ Dodonova, S. O.; Diestelkoetter-Bachert, P.; von Appen, A.; Hagen, W. J. H.; Beck, R.; Beck, M.; Wieland, F.; Briggs, J. a. G. (2015-07-10). "VESICULAR TRANSPORT. A structure of the COPI coat and the role of coat proteins in membrane vesicle assembly". Science. 349 (6244): 195–198. doi:10.1126/science.aab1121. ISSN   1095-9203. PMID   26160949. S2CID   42823630.
  14. ↑ Faini, Marco; Prinz, Simone; Beck, Rainer; Schorb, Martin; Riches, James D.; Bacia, Kirsten; Brügger, Britta; Wieland, Felix T.; Briggs, John A. G. (2012-06-15). "The structures of COPI-coated vesicles reveal alternate coatomer conformations and interactions" (PDF). Science. 336 (6087): 1451–1454. Bibcode:2012Sci...336.1451F. doi:10.1126/science.1221443. ISSN   1095-9203. PMID   22628556. S2CID   45327176.
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