Yeast Irc6p is a novel type of conserved clathrin coat accessory factor related to small G proteins

• Published in: Molecular biology of the cell 2012-11, Vol.23 (22), p.4416-4429
• Main Authors: Gorynia, Sabine, Lorenz, Todd C, Costaguta, Giancarlo, Daboussi, Lydia, Cascio, Duilio, Payne, Gregory S
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Vesicular Transport - chemistry; Adaptor Proteins, Vesicular Transport - metabolism; Adaptor Proteins, Vesicular Transport - physiology; ADP-Ribosylation Factor 1 - chemistry; Amino Acid Sequence; Biological Transport; Clathrin - metabolism; Conserved Sequence; Crystallography, X-Ray; Endosomes - metabolism; Molecular Sequence Data; Monomeric GTP-Binding Proteins - chemistry; Monomeric GTP-Binding Proteins - metabolism; Monomeric GTP-Binding Proteins - physiology; Protein Interaction Mapping; Protein Structure, Tertiary; rab GTP-Binding Proteins - chemistry; rab GTP-Binding Proteins - genetics; rab GTP-Binding Proteins - metabolism; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Saccharomyces cerevisiae Proteins - physiology; Sequence Alignment; trans-Golgi Network - metabolism; trans-Golgi Network - physiology
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E12-07-0507

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.