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

ELife
Brian C RichardsonJ Christopher Fromme

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.

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Citations

Jul 21, 2016·Journal of Molecular Cell Biology·Rong WangJianping Ding
Mar 9, 2018·The Journal of Biological Chemistry·Steve L Halaby, J Christopher Fromme
Jul 28, 2016·Small GTPases·Agata NawrotekJacqueline Cherfils
Feb 14, 2017·PLoS Pathogens·Hayet LabbaouiMartine Bassilana
Oct 5, 2019·F1000Research·Andrew B Goryachev, Marcin Leda
Jan 14, 2020·Developmental Cell·John J H ShinChristopher J R Loewen
Apr 9, 2021·Structure·Aaron M N Joiner, J Christopher Fromme
Aug 13, 2021·The Journal of Cell Biology·Ann-Christin BorchersChristian Ungermann

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Methods Mentioned

BETA
GTPases
nucleotide exchange
GTPase
X-ray
gel filtration
pulldown
2-hybrid
light

Software Mentioned

BUNCH
ASTRA
ImageJ
PHENIX
MUSCLE
Coot
CRYSOL
CORAL
BioXTAS RAW
SoftWoRx

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