COPI is a coatomer , a protein complex 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 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 .
20-430: Ashirbad TRF Ggv Ggb Coat protein, or COPI, is an ADP ribosylation factor (ARF)-dependent protein involved in membrane traffic. COPI was first identified in retrograde traffic from the cis -Golgi to the rough endoplasmic reticulum (ER) 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
40-885: A new GTP molecule in place of a bound GDP. Other proteins interact with ARF, depending upon whether or not it is bound to GTP or GDP. The active form, ARF*GTP, binds to vesicle coat proteins and adaptors, including coat protein I (COPI) and various phospholipids. The inactive form is only known to bind to a class of transmembrane proteins. Different types of ARF bind specifically different kinds of effector proteins. There are currently 6 known mammalian ARF proteins, which are divided into three classes of ARFs: ARFs are small proteins of approximately 20 kDa in size. They contain two switch regions, which change relative positions between cycles of GDP/GTP-binding. ARFs are frequently myristoylated in their N-terminal region, which contributes to their membrane association. Human genes encoding proteins containing this domain include: COPI COPI
60-635: A regulatory subunit that control coat assembly in coat protein I ( COPI ), and clathrin-coated vesicles . ARF binds to two forms of the guanosine nucleotide, guanosine triphosphate (GTP) and guanosine diphosphate (GDP). The shape of the ARF molecule is dependent upon the form to which it is bound, allowing it to serve in a regulatory capacity. ARF requires assistance from other proteins in order to switch between binding to GTP and GDP. GTPase activating proteins (GAPs) force ARF to hydrolyze bound GTP to GDP, and Guanine nucleotide exchange factors force ARF to adopt
80-453: A two-residue register shift that pulls switch 1 and switch 2 up, restoring an active conformation that can bind GTP. In this conformation, the interswitch projects out of the protein and extrudes the N-terminal hasp by occluding its binding pocket. ARFs regularly associate with two types of protein, those involved in catalyzing GTP/GDP exchange, and those that serve other functions. ARFs act as
100-468: A unique conformational change that affects the beta2beta3 strands connecting switch 1 and switch 2 (interswitch) and also the amphipathic helical N-terminus. In GDP-bound Arf1 and Arf6, the interswitch is retracted and forms a pocket to which the N-terminal helix binds, the latter serving as a molecular hasp to maintain the inactive conformation. In the GTP-bound form of these proteins, the interswitch undergoes
120-496: Is a coatomer , a protein complex 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 is retrograde transport , in contrast to the anterograde transport associated with the COPII protein. The name "COPI" refers to
140-454: 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
160-514: 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
180-552: 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. 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
200-436: The cis -Golgi to the rough endoplasmic reticulum (ER) 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
220-585: 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. The small ADP ribosylation factor (Arf) GTP-binding proteins are major regulators of vesicle biogenesis in intracellular traffic. They are
SECTION 10
#1732927844253240-477: 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
260-592: 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; instead, they are linked to one another via the γζβδ-COP subcomplexes, forming an interconnected assembly . The triads are linked together with contacts of variable valence making up four different types of contacts. ADP ribosylation factor ADP ribosylation factors ( ARFs ) are members of
280-423: 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
300-415: 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
320-414: The cis-Golgi to the ER. 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
340-437: The founding members of a growing family that includes Arl (Arf-like), Arp (Arf-related proteins) and the remotely related Sar (Secretion-associated and Ras-related) proteins. Arf proteins cycle between inactive GDP-bound and active GTP-bound forms that bind selectively to effectors. The classical structural GDP/GTP switch is characterised by conformational changes at the so-called switch 1 and switch 2 regions, which bind tightly to
360-488: The gamma-phosphate of GTP but poorly or not at all to the GDP nucleotide. Structural studies of Arf1 and Arf6 have revealed that although these proteins feature the switch 1 and 2 conformational changes, they depart from other small GTP-binding proteins in that they use an additional, unique switch to propagate structural information from one side of the protein to the other. The GDP/GTP structural cycles of human Arf1 and Arf6 feature
380-423: 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
400-429: 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 . Ashirbad TRF Ggv Ggb Coat protein, or COPI, is an ADP ribosylation factor (ARF)-dependent protein involved in membrane traffic. COPI was first identified in retrograde traffic from
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