Conserved structural motifs in intracellular trafficking pathways: structure of the gammaCOP appendage domain.
The formation of coated vesicles is a fundamental step in many intracellular trafficking pathways. COPI and clathrin represent two important and distinct sets of vesicle coating machinery, involved primarily in mediating intra-Golgi and endocytic transport, respectively. Here we identify an important functional region at the carboxyl terminus of the gamma subunit of the COPI complex (gammaCOP) and describe the X-ray crystal structure of this domain at 2.3 A resolution. This domain of gammaCOP exhibits unexpected structural similarity to the carboxyl-terminal appendage domains of the alpha and beta subunits of the AP2 adaptor proteins, integral components of clathrin-coated vesicles. The remarkable structural conservation exhibited by the gammaCOP appendage domain, coupled with functional data and primary sequence analysis, supports a model of COPI function with significant structural and mechanistic parallels to vesicular transport by the clathrin/AP2 system.
Hoffman
Gregory R
GR
Department of Molecular Medicine, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Rahl
Peter B
PB
Collins
Ruth N
RN
Cerione
Richard A
RA
D033962:Adaptor Protein Complex 2 / Q000378:metabolism; D020816:Amino Acid Motifs / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D018699:Coated Vesicles / Q000378:metabolism*; D020756:Coatomer Protein; D017124:Conserved Sequence / Q000502:physiology*; D005057:Eukaryotic Cells / Q000378:metabolism; D019143:Evolution, Molecular; D007424:Intracellular Fluid / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010802:Phylogeny; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D033962:Adaptor Protein Complex 2; D002352:Carrier Proteins; D020756:Coatomer Protein