title: Structural basis for membrane binding and remodeling by the exomer secretory vesicle cargo adaptor.
abstract: Cargo adaptor subunits of vesicle coat protein complexes sort transmembrane proteins to distinct membrane compartments in eukaryotic cells. The exomer complex is the only cargo adaptor known to sort proteins at the trans-Golgi network into secretory vesicles. Exomer function is regulated by the Arf1 GTPase, a master regulator of trafficking at the Golgi. We report the structure of exomer bound to two copies of Arf1. Exomer interacts with each Arf1 molecule via two surfaces, one of which is a noncanonical interface that regulates GTP hydrolysis. The structure uncovers an unexpected membrane-proximal hydrophobic element that exomer uses in cooperation with Arf1 to remodel membranes. Given the constrained motion of the exomer hinge region, we envision that exomer dynamically positions multiple membrane insertion elements to drive membrane fission. In contrast to other known cargo adaptors, exomer therefore couples two functions, cargo sorting and membrane fission, into a single complex.
authors.affiliation: Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Jon E
authors.initials: JE
authors.lastname: Paczkowski
authors.affiliation: Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA. Electronic address: jcf14@cornell.edu.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Fromme
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism*; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D015966:Gene Expression Regulation, Fungal; D006056:Golgi Apparatus / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry; D006868:Hydrolysis; D008969:Molecular Sequence Data; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D006160:Guanosine Triphosphate; D020823:ADP-Ribosylation Factor 1