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TitleSec7 regulatory domains scaffold autoinhibited and active conformations.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 121, Issue 10, Page e2318615121, Year 2024
Publish dateMar 5, 2024
AuthorsBryce A Brownfield / Brian C Richardson / Steve L Halaby / J Christopher Fromme /
PubMed AbstractThe late stages of Golgi maturation involve a series of sequential trafficking events in which cargo-laden vesicles are produced and targeted to multiple distinct subcellular destinations. Each of ...The late stages of Golgi maturation involve a series of sequential trafficking events in which cargo-laden vesicles are produced and targeted to multiple distinct subcellular destinations. Each of these vesicle biogenesis events requires activation of an Arf GTPase by the Sec7/BIG guanine nucleotide exchange factor (GEF). Sec7 localization and activity is regulated by autoinhibition, positive feedback, and interaction with other GTPases. Although these mechanisms have been characterized biochemically, we lack a clear picture of how GEF localization and activity is modulated by these signals. Here, we report the cryogenic electron microscopy structure of full-length Sec7 in its autoinhibited form, revealing the architecture of its multiple regulatory domains. We use functional experiments to determine the basis for autoinhibition and use structural predictions to produce a model for an active conformation of the GEF that is supported empirically. This study therefore elucidates the conformational transition that Sec7 undergoes to become active on the organelle membrane surface.
External linksProc Natl Acad Sci U S A / PubMed:38416685 / PubMed Central
MethodsEM (single particle)
Resolution3.7 - 5.3 Å
Structure data

42135

8ucq

EMDB-42135, PDB-8ucq:
CryoEM structure of Sec7 autoinhibited conformation
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-42182: Focused map of Sec7 monomer autoinhibited conformation
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-42183: Consensus map of Sec7 dimer autoinhibited conformation
Method: EM (single particle) / Resolution: 5.3 Å

Source
  • thermothielavioides terrestris (fungus)
KeywordsPROTEIN TRANSPORT / GEF / Exchange Factor / Golgi

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