Yeast Irc6p is a novel type of conserved clathrin coat accessory factor related to small G proteins.
Publication Type:Journal Article
Source:Mol Biol Cell, Volume 23, Issue 22, p.4416-29 (2012)
Keywords:Adaptor Proteins, Vesicular Transport, ADP-Ribosylation Factor 1, Amino Acid Sequence, Biological Transport, Clathrin, Conserved Sequence, Crystallography, X-Ray, Endosomes, Molecular Sequence Data, Monomeric GTP-Binding Proteins, Protein Interaction Mapping, Protein Structure, Tertiary, rab GTP-Binding Proteins, Saccharomyces cerevisiae Proteins, Sequence Alignment, trans-Golgi Network
<p>Clathrin coat accessory proteins play key roles in transport mediated by clathrin-coated vesicles. Yeast Irc6p and the related mammalian p34 are putative clathrin accessory proteins that interact with clathrin adaptor complexes. We present evidence that Irc6p functions in clathrin-mediated traffic between the trans-Golgi network and endosomes, linking clathrin adaptor complex AP-1 and the Rab GTPase Ypt31p. The crystal structure of the Irc6p N-terminal domain revealed a G-protein fold most related to small G proteins of the Rab and Arf families. However, Irc6p lacks G-protein signature motifs and high-affinity GTP binding. Also, mutant Irc6p lacking candidate GTP-binding residues retained function. Mammalian p34 rescued growth defects in irc6 cells, indicating functional conservation, and modeling predicted a similar N-terminal fold in p34. Irc6p and p34 also contain functionally conserved C-terminal regions. Irc6p/p34-related proteins with the same two-part architecture are encoded in genomes of species as diverse as plants and humans. Together these results define Irc6p/p34 as a novel type of conserved clathrin accessory protein and founding members of a new G protein-like family.</p>