title: The exomer cargo adaptor structure reveals a novel GTPase-binding domain.
abstract: Cargo adaptors control intracellular trafficking of transmembrane proteins by sorting them into membrane transport carriers. The COPI, COPII, and clathrin cargo adaptors are structurally well characterized, but other cargo adaptors remain poorly understood. Exomer is a specialized cargo adaptor that sorts specific proteins into trans-Golgi network (TGN)-derived vesicles in response to cellular signals. Exomer is recruited to the TGN by the Arf1 GTPase, a universally conserved trafficking regulator. Here, we report the crystal structure of a tetrameric exomer complex composed of two copies each of the Chs5 and Chs6 subunits. The structure reveals the FN3 and BRCT domains of Chs5, which together we refer to as the FBE domain (FN3-BRCT of exomer), project from the exomer core complex. The overall architecture of the FBE domain is reminiscent of the appendage domains of other cargo adaptors, although it exhibits a distinct topology. In contrast to appendage domains, which bind accessory factors, we show that the primary role of the FBE domain is to bind Arf1 for recruitment of exomer to membranes.
authors.affiliation: Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
authors.forename: Jon E
authors.initials: JE
authors.lastname: Paczkowski
authors.forename: Brian C
authors.initials: BC
authors.lastname: Richardson
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Strassner
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Fromme
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002687:Chitin Synthase / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006056:Golgi Apparatus / Q000378:metabolism; D008081:Liposomes; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C509470:CHS6 protein, S cerevisiae; D008081:Liposomes; D029701:Saccharomyces cerevisiae Proteins; C491360:CHS5 protein, S cerevisiae; D002687:Chitin Synthase; D020823:ADP-Ribosylation Factor 1