The Sec7 N-terminal regulatory domains facilitate membrane-proximal activation of the Arf1 GTPase

Brian C. Richardson, Steve L. Halaby, Margaret A. Gustafson, J. Christopher Fromme

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere12411
JournaleLife
Volume5
Issue numberJANUARY2016
DOIs
StatePublished - Jan 14 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Richardson et al.

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