This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We will determine the structure of the complex between the Rab GTPase Sec4 and its guanine exchange factor Sec2. The structure is expected to yield the first mechanistic insights as to how guanine exchange is catalysed for the Rab family of GTPases. There is at present one known structure for a GEF that acts on a Rab GTPase (Vps9 domain of Rabex5) and no structure of a GEF in complex with a Rab GTPase. Our mechanistic insights will be tested by mutagenesis. The Sec4 GTPase is pivotal in the assembly of the exocyst tethering complex, which plays a key role in exocytosis.
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