a Flexible Hinge Domain

rll complexes, which serve as intermediary adaptors between the protein cargo and the machinery mediating the physical pro-Chs5 binding of Arf1 are mediated by distinct domains (Pacz-kowski et al., 2012). In contrast, Chs6 exhibits a complex foldtively (Bi et al., 2002; Yu et al., 2012); and Vps26/29/35 of the more divergent retromer complex (Hierro et al., 2007). Exomer is a recently discovered cargo adaptor (Sanchatjate different ChAP, Bch1. The structure of the Chs5 dimerization interface is revealed to be a noncanonical trans b sandwich. By comparing small-angle X-ray scattering (SAXS) and X-rayand Schekman, 2006; Trautwein et al., 2006; Wang et al., 2006a) possessing several unusual properties. Exomer acts in the poorly characterized direct trans-Golgi network (TGN) to crystallographic data, we find that this motif exhibits an unex-pected flexibility in solution with implications for exomer function as a cargo adaptor in a heterogenous membrane milieu.cess of vesicle formation. By directly binding both cytoplasmic domains of transmembrane proteins and vesicle coats, these cargo adaptors package their cargo into specific vesicles, and indeed are core components of the vesicle coats themselves (Matsuoka et al., 1998; Robinson and Bonifacino, 2001; Takatsu et al., 2001). Structurally well-characterized examples of cargo adaptors include the GGA and AP adaptors for the clathrin coat (Owen et al., 2004); the core components bd/gz-COP and Sec23/24 of the unrelated COPI and COPII complexes, respec-topology in which an extended tetratricopeptide repeat (TPR) region, thought to be largely invariant between ChAPs (Rocken-bauch et al., 2012), forms the binding surface for Chs5. However, extensive crystal packing interactions strained the N-terminal Chs5 dimerization interface to such a degree that little could be concluded regarding the interactions mediating tetrameriza-tion (Paczkowski et al., 2012). Here, we present the crystal structure of a tetrameric exomer complex, composed of the Chs5 N-terminal domains and atemporally in eukaryotic cells by the action of soluble protein in which exomer tetramerization, Chs5 binding of ChAPs, andThe Exomer Cargo Adapt