The Exomer Cargo Adaptor Features a Flexible Hinge Domain

SummaryExomer is a cargo adaptor that mediates the sorting of specific plasma membrane proteins into vesicles at the trans-Golgi network. Cargo adaptors must bind to multiple partners, including their cargo, regulatory proteins, and the membrane surface. During biogenesis of a vesicle, the membrane makes a transition from a relatively flat surface to one of high curvature, requiring cargo adaptors to somehow maintain protein-protein and protein-membrane interactions on a changing membrane environment. Here, we present the crystal structure of a tetrameric Chs5/Bch1 exomer complex and use small-angle X-ray scattering to demonstrate its flexibility in solution. The structural data suggest that the complex flexes primarily around the dimeric N-terminal domain of the Chs5 subunits, which adopts a noncanonical β sandwich fold. We propose that this flexible hinge domain enables exomer to maintain interactions in the context of a dynamic membrane environment.

► We determined the Chs5/Bch1 exomer complex crystal structure to 2.9 Å
► The Chs5 dimerization domain is a noncanonical trans β sandwich
► The exomer is flexible about the Chs5 dimerization domain
► Flexibility may facilitate function on dynamic membranes