Abstract
Sec15, a component of the exocyst, recognizes vesicle-associated Rab GTPases, helps target transport vesicles to the budding sites in yeast and is thought to recruit other exocyst proteins. Here we report the characterization of a 35-kDa fragment that comprises most of the C-terminal half of Drosophila melanogaster Sec15. This C-terminal domain was found to bind a subset of Rab GTPases, especially Rab11, in a GTP-dependent manner. We also provide evidence that in fly photoreceptors Sec15 colocalizes with Rab11 and that loss of Sec15 affects rhabdomere morphology. Determination of the 2.5-A crystal structure of the C-terminal domain revealed a novel fold consisting of ten alpha-helices equally distributed between two subdomains (N and C subdomains). We show that the C subdomain, mainly via a single helix, is sufficient for Rab binding.
