title: Yeast Irc6p is a novel type of conserved clathrin coat accessory factor related to small G proteins.
abstract: 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.
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Sabine
authors.initials: S
authors.lastname: Gorynia
authors.forename: Todd C
authors.initials: TC
authors.lastname: Lorenz
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Costaguta
authors.forename: Lydia
authors.initials: L
authors.lastname: Daboussi
authors.forename: Duilio
authors.initials: D
authors.lastname: Cascio
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Payne
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000737:chemistry; D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D001692:Biological Transport; D002966:Clathrin / Q000378:metabolism; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D011992:Endosomes / Q000378:metabolism; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016415:Sequence Alignment; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism / Q000502:physiology
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; C580927:Irc6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C087905:YPT31 protein, S cerevisiae; D020823:ADP-Ribosylation Factor 1; D020559:Monomeric GTP-Binding Proteins; D020691:rab GTP-Binding Proteins