Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p.
The GATE-16 protein participates in intra-Golgi transport and can associate with the N-ethylmaleimide-sensitive fusion protein and with Golgi SNAREs. The yeast ortholog of GATE-16 is the autophagocytosis factor Aut7p. GATE-16 is also closely related to the GABA receptor-associated protein (GABARAP), which has been proposed to cluster neurotransmitter receptors by mediating interaction with the cytoskeleton, and to the light chain-3 subunit of the neuronal microtubule-associated protein complex. Here, we present the crystal structure of GATE-16 refined to 1.8 A resolution. GATE-16 contains a ubiquitin fold decorated by two additional N-terminal helices. Proteins with strong structural similarity but no detectable sequence homology to GATE-16 include Ras effectors that mediate diverse downstream functions, but each interacts with Ras by forming pseudo-continuous beta-sheets. The GATE-16 surface suggests that it binds its targets in a similar manner. Moreover, a second potential protein-protein interaction site on GATE-16 may explain the adapter activity observed for members of the GATE-16 family.
Paz
Y
Y
Department of Structural Biology and Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Elazar
Z
Z
Fass
D
D
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000071190:Autophagy-Related Protein 8 Family; D002352:Carrier Proteins / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism*; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014452:Ubiquitins / Q000737:chemistry; D018631:ras Proteins / Q000378:metabolism
C113757:ATG8 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; D000071190:Autophagy-Related Protein 8 Family; D002352:Carrier Proteins; C498698:GABARAPL2 protein, human; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D018631:ras Proteins