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COPII

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For the 1996 United Nations Climate Change Conference in Geneva, Switzerland, see COP 2 (climate conference).
Sec23 homolog A
Ribbon diagram of the crystallographic structure of the COPII heterodimer of Sec23 and Sec24. Alpha helices are in red and the beta sheets are in yellow.[1]
Identifiers
SymbolSEC23A
NCBI gene856311
HGNC10701
OMIM610511
PDB1M2V
RefSeqNM_006364
UniProtQ15436
Other data
LocusChr. 14 q21.1
Search for
StructuresSwiss-model
DomainsInterPro
SEC24 family, member A
Identifiers
SymbolSEC24A
NCBI gene10802
HGNC10703
OMIM607183
PDB1M2V
RefSeqXM_001132082
UniProtO95486
Other data
LocusChr. 5 q31.1
Search for
StructuresSwiss-model
DomainsInterPro

COPII is a coatomer, a type of vesicle coat protein that transports proteins from the rough endoplasmic reticulum to the Golgi apparatus.[2][3] 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.

Function

Assembly

Coat assembly is initiated when the cytosolic Ras GTPase Sar1 is activated by its guanine nucleotide exchange factor Sec12.[4] Activated Sar1-GTP inserts itself into the ER membrane, binding preferentially to areas of membrane curvature. As Sar1-GTP inserts into the membrane, it recruits Sec23 and Sec24 to make up the inner cage.[4] Once the inner coat is assembled, the outer coat proteins Sec13 and Sec31 are recruited to the budding vesicle.[4]

Some proteins are found to be responsible for selectively packaging cargos into COPII vesicles. More recent research suggests the Sec23/Sec24-Sar1 complex participates in cargo selection.[5] For example, Erv29p in Saccharomyces cerevisiae is found to be necessary for packaging glycosylated pro-α-factor.[6]

Sec24 proteins recognize various cargo proteins, packaging them into the budding vesicles.

After the COPII vesicle forms, the COPII coat proteins remain assembled to allow the Sec23/Sec24 complex to interact with a tethering factor on the Cis-Golgi membrane. When the COPII vesicle is in close proximity to the Cis-Golgi membrane, it sheds its coat and the components are recycled to function for another vesicle.

Structure

The COPII coat consists of an inner layer – a flexible meshwork of Sar1, Sec23, and Sec24 – and an outer layer made of Sec13 and Sec31.[4] Sar1 resembles other Ras-family GTPases, with a core of six beta strands flanked by three alpha helices, and two flexible "switch domains". Unlike other Ras GTPases, Sar1 inserts into membranes via an N-terminal helix (rather than myristoylation or prenylation).[4]

These coat proteins are necessary but insufficient to direct or dock the vesicle to the correct target membrane. SNARE, cargo, and other proteins are also needed for these processes to occur.

Pre-budding complex (composed of Sar1-GTP and Sec23/24) recruits the flexible Sec13p/31p complex, characterized by polymerization of the Sec13/31 complex with other Sec13/31 complexes to form a cuboctahedron with a broader lattice than its Clathrin vesicle analog. The formation of the cuboctahedron deforms the ER membrane and detaches the COPII vesicle (alongside cargo proteins and v-SNAREs), completing the COPII vesicle budding process.[5]


Evolution

In mammals there are two Sar1 genes: Sar1A and Sar1B. In cultured mammalian cells the two Sar1 genes appear redundant; however, in animals Sar1B is uniquely required for the formation of large (over 1 micrometer across) COPII-coated vesicles. Some variations in Sar1B cause Chylomicron retention disease.[4]

Similarly, mammals express two Sec23 genes, Sec23A and Sec23B. The two Sec23 isoforms have identical function but are expressed in different body tissues. A Sec23A variant causes Cranio-lenticulo-sutural dysplasia, while Sec23B variants are associated with anemia and some cancers.[4] Both Sec23 proteins can interact with any of the four Sec24 proteins: Sec24A, Sec24B, Sec24C, and Sec24D.[4]

Conformational changes

CopII has three specific binding sites that can each be complexed. The adjacent picture (Sed5) uses the Sec22 t-SNARE complex to bind. This site is more strongly bound, and therefore is more favored. (Embo)

Crystal structures of CopII
  • Conformation of the CopII protein complexed with the snare protein Bet1 (PDB: 1PCX​).[7]
    Conformation of the CopII protein complexed with the snare protein Bet1 (PDB: 1PCX​).[7]
  • Conformation of the CopII protein that is complexed with the snare protein Sed5 (PDB: 1PD0​).[7]
    Conformation of the CopII protein that is complexed with the snare protein Sed5 (PDB: 1PD0​).[7]

Research

Mutations the threonine at position 39 to asparagine generates a dominant negative Sar1A bound permanently to GDP; mutating histidine 79 to glycine generates a constitutively active Sar1A, with GTP hydrolysis slowed dramatically.[4]

See also

References

  1. ^ PDB: 3EH1​; Mancias JD, Goldberg J (November 2008). "Structural basis of cargo membrane protein discrimination by the human COPII coat machinery". EMBO J. 27 (21): 2918–28. doi:10.1038/emboj.2008.208. PMC 2580787. PMID 18843296.
  2. ^ Lee MC, Miller EA (August 2007). "Molecular mechanisms of COPII vesicle formation". Semin. Cell Dev. Biol. 18 (4): 424–34. doi:10.1016/j.semcdb.2007.06.007. PMID 17686639.
  3. ^ Hughes H, Stephens DJ (February 2008). "Assembly, organization, and function of the COPII coat". Histochem. Cell Biol. 129 (2): 129–51. doi:10.1007/s00418-007-0363-x. PMC 2228377. PMID 18060556.
  4. ^ a b c d e f g h i Peotter J, Kasberg W, Pustova I, Audhya A (July 2019). "COPII-mediated trafficking at the ER/ERGIC interface". Traffic. 20 (7): 491–503. doi:10.1111/tra.12654. PMC 6640837. PMID 31059169.
  5. ^ a b Fath S, Mancias JD, Bi X, Goldberg J (June 2007). "Structure and organization of coat proteins in the COPII cage". Cell. 129 (7): 1325–36. doi:10.1016/j.cell.2007.05.036. PMID 17604721. S2CID 10692166.
  6. ^ Belden WJ, Barlowe C (November 2001). "Role of Erv29p in collecting soluble secretory proteins into ER-derived transport vesicles". Science. 294 (5546): 1528–31. Bibcode:2001Sci...294.1528B. doi:10.1126/science.1065224. PMID 11711675. S2CID 29870942.
  7. ^ a b 1PCX​; 1PD0​; Mossessova E, Bickford LC, Goldberg J (August 2003). "SNARE selectivity of the COPII coat". Cell. 114 (4): 483–95. doi:10.1016/S0092-8674(03)00608-1. PMID 12941276. S2CID 11379372.
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