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Publication Abstract from PubMed

The Golgi complex is the central sorting compartment of eukaryotic cells. Arf guanine nucleotide exchange factors (Arf-GEFs) regulate virtually all traffic through the Golgi by activating Arf GTPase trafficking pathways. The Golgi Arf-GEFs contain multiple autoregulatory domains, but the precise mechanisms underlying their function remain largely undefined. We report a crystal structure revealing that the N-terminal DCB and HUS regulatory domains of the Arf-GEF Sec7 form a single structural unit. We demonstrate that the established role of the N-terminal region in dimerization is not conserved; instead, a C-terminal autoinhibitory domain is responsible for dimerization of Sec7. We find that the DCB/HUS domain amplifies the ability of Sec7 to activate Arf1 on the membrane surface by facilitating membrane insertion of the Arf1 amphipathic helix. This enhancing function of the Sec7 N-terminal domains is consistent with the high rate of Arf1-dependent trafficking to the plasma membrane necessary for maximal cell growth.

The Sec7 N-terminal regulatory domains facilitate membrane-proximal activation of the Arf1 GTPase.,Richardson BC, Halaby SL, Gustafson MA, Fromme JC Elife. 2016 Jan 14;5. pii: e12411. doi: 10.7554/eLife.12411. PMID:26765562^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.