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PreprintCited by 22Cellular transport and secretionProtein Kinase Regulation and GTPase SignalingReceptor Mechanisms and Signaling

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Structural basis for activation of Arf1 at the Golgi complex

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Muccini, Arnold J., Gustafson, Margaret A., Fromme, J. Christopher·2022·Cell Reports
DOI 10.1101/2022.05.04.490673PMC PMC9469209

Preprint — published as 10.1016/j.celrep.2022.111282

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Abstract

Summary: The Golgi complex is the central sorting station of the eukaryotic secretory pathway. Traffic through the Golgi requires activation of Arf GTPases that orchestrate cargo sorting and vesicle formation by recruiting an array of effector proteins. Arf activation and Golgi membrane association is controlled by large guanine nucleotide exchange factors (GEFs) possessing multiple conserved regulatory domains. Here we present cryoEM structures of full-length Gea2, the yeast paralog of the human Arf-GEF GBF1, that reveal the organization of these regulatory domains and explain how Gea2 binds to the Golgi membrane surface. We find the GEF domain adopts two different conformations compatible with different stages of the Arf activation reaction. The structure of a Gea2-Arf1 activation intermediate suggests the movement of the GEF domain primes Arf1 for membrane insertion upon GTP binding. We propose that conformational switching of Gea2 during the nucleotide exchange reaction promotes membrane insertion of Arf1.

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Metadata

Authors
Muccini, A. J., Gustafson, M. A., & Fromme, J. C.
Affiliations
Cornell University (US)
Corresponding author
Fromme, J. Christopher
ORCID
Venue
Cell Reports
Publisher
openRxiv
Published
2022-05-04
Volume
40
Issue
9
Pages
111282-111282
ISSN
2211-1247 (ISSN-L)
DOI
10.1101/2022.05.04.490673
PMC
PMC9469209
OpenAlex
W4293574539
Cited by
22
References
1
Citations by year
2026: 4 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 2
FWCI
2.41
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cell Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
Funders
  • National Science Foundation (1719875)
  • National Institutes of Health (DMR-1719875)
  • Cornell Center for Materials Research (DMR‐1719875, 1719875)
  • National Institute of General Medical Sciences (R35GM136258)
  • Division of Materials Research (DMR-1719875, 1719875)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
Arf1, GBF1, guanine nucleotide exchange factor, Golgi apparatus, secretory pathway, membrane insertion, conformational switching, nucleotide exchange, yeast
MeSH terms
Golgi Apparatus, Saccharomyces cerevisiae, Cryoelectron Microscopy, Guanine Nucleotide Exchange Factors, ADP-Ribosylation Factors, ADP-Ribosylation Factor 1, Protein Transport, Saccharomyces cerevisiae Proteins

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