ArticleProceedings of the National Academy of Sciences of the United States of America2007
Crystal structure of the Sec4p.Sec2p complex in the nucleotide exchanging intermediate state.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Cryo-EM structure of the human MON1A-CCZ1-RAB7A complex provides insights into nucleotide exchange mechanism.Life metabolism · 2025Article
- Structure of the metazoan Rab7 GEF complex Mon1-Ccz1-Bulli.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Small GTPase FoSec4-Mediated Protein Secretion Is Important for Polarized Growth, Reproduction and Pathogenicity in the Banana Fusarium Wilt FungusJournal of fungi (Basel, Switzerland) · 2022Article
- Article
- Structural communication between the GTPase Sec4p and its activator Sec2p: Determinants of GEF activity and early deformations to nucleotide release.Computational and structural biotechnology journal · 2022Article
- Structural Insights into the Regulation Mechanism of Small GTPases by GEFs.Molecules (Basel, Switzerland) · 2019Review
- Structural basis of guanine nucleotide exchange for Rab11 by SH3BP5.Life science alliance · 2019Article
- Structural determinants of Rab11 activation by the guanine nucleotide exchange factor SH3BP5.Nature communications · 2018Article
- Molecular control of Rab activity by GEFs, GAPs and GDI.Small GTPases · 2018Review
- Architecture and mechanism of the late endosomal Rab7-like Ypt7 guanine nucleotide exchange factor complex Mon1-Ccz1.Nature communications · 2017Article
- AFM/TIRF force clamp measurements of neurosecretory vesicle tethers reveal characteristic unfolding steps.PloS one · 2017Article
- A pull-down procedure for the identification of unknown GEFs for small GTPases.Small GTPases · 2016Article
- New insights into the molecular mechanism of the Rab GTPase Sec4p activation.BMC structural biology · 2015Article
- The Mon1-Ccz1 GEF activates the Rab7 GTPase Ypt7 via a longin-fold-Rab interface and association with PI3P-positive membranes.Journal of cell science · 2014Article
- The beginning of the end: how scaffolds nucleate autophagosome biogenesis.Trends in cell biology · 2014Review
- Intermediates in the guanine nucleotide exchange reaction of Rab8 protein catalyzed by guanine nucleotide exchange factors Rabin8 and GRAB.The Journal of biological chemistry · 2013Article
- Bicaudal-D uses a parallel, homodimeric coiled coil with heterotypic registry to coordinate recruitment of cargos to dynein.Genes & development · 2013Article
- A Rab8 guanine nucleotide exchange factor-effector interaction network regulates primary ciliogenesis.The Journal of biological chemistry · 2012Article
- Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Phosphorylation provides a negative mode of regulation for the yeast Rab GTPase Sec4p.PloS one · 2011Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vesicular transport during exocytosis is regulated by Rab GTPase (Sec4p in yeast), which is activated by a guanine nucleotide exchange factor (GEF) called Sec2p. Here, we report the crystal structure of the Sec2p GEF domain in a complex with the nucleotide-free Sec4p at 2.7 A resolution. Upon complex formation, the Sec2p helices approach each other, flipping the side chain of Phe-109 toward Leu-104 and Leu-108 of Sec2p. These three residues provide a hydrophobic platform to attract the side chains of Phe-49, Ile-53, and Ile-55 in the switch I region as well as Phe-57 and Trp-74 in the interswitch region of Sec4p. Consequently, the switch I and II regions are largely deformed, to create a flat hydrophobic interface that snugly fits the surface of the Sec2p coiled coil. These drastic conformational changes disrupt the interactions between switch I and the bound guanine nucleotide, which facilitates the GDP release. Unlike the recently reported 3.3 A structure of the Sec4p.Sec2p complex, our structure contains a phosphate ion bound to the P-loop, which may represent an intermediate state of the nucleotide exchange reaction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.