The Guanine Nucleotide-Binding Switch in Three Dimensions
Abstract
Guanine nucleotide–binding proteins regulate a variety of processes, including sensual perception, protein synthesis, various transport processes, and cell growth and differentiation. They act as molecular switches and timers that cycle between inactive guanosine diphosphate (GDP)–bound and active guanosine triphosphate (GTP)–bound states. Recent structural studies show that the switch apparatus itself is a conserved fundamental module but that its regulators and effectors are quite diverse in their structures and modes of interaction. Here we will try to define some underlying principles.
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Vetter et al. mention that different KRAS mutations are grouped into four categories based on their effects on GTP hydrolysis, nucleotide exchange, and effector protein interactions.
“Vetter et al. mention that different KRAS mutations are grouped into four categories based on their effects on GTP hydrolysis, nucleotide exchange, and effector protein interactions [152].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [152]
These rapid exchange mutations may deplete the activity of GEF, thereby desensitizing cancer cells to GEF inhibition.
“However, these rapid exchange mutations may deplete the activity of GEF, thereby desensitizing cancer cells to GEF inhibition [152–154].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [152]
Rapid exchange mutants can synergize with GEF to produce extremely high levels of nucleotide exchange.
“Rapid exchange mutants can synergize with GEF to produce extremely high levels of nucleotide exchange.”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [152]
KRAS (G13D) enhances nucleotide exchange.
“For example, KRAS (G13D) enhances nucleotide exchange.”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [152]
KRAS binds GDP in its inactive state and GTP in its active state.
“The small GTPase protein KRAS is a signal-transducing protein, which binds GDP in its inactive state and GTP in its active state [1].”
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- Authors
- Vetter, I. R., & Wittinghofer, A.
- Affiliations
- Max Planck Institute of Molecular Physiology (DE)
- Venue
- Science
- Published
- 2001-11-09
- Volume
- 294
- Issue
- 5545
- Pages
- 1299-1304
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2156571424
- Cited by
- 1,875
- References
- 69
- Citations by year
- 2026: 58 · 2025: 63 · 2024: 102 · 2023: 69 · 2022: 83 · 2021: 78 · 2020: 95 · 2019: 80 · 2018: 72 · 2017: 78 · 2016: 76 · 2015: 82 · 2014: 71 · 2013: 89 · 2012: 87
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- G proteins, molecular switches, protein structure, G protein structure, signal transduction, protein structure-function relationship
- MeSH terms
- Allosteric Regulation, Binding Sites, Guanosine Diphosphate, Guanosine Triphosphate, Hydrolysis, Models, Molecular, Protein Conformation, Protein Structure, Tertiary, GTP-Binding Proteins, GTP Phosphohydrolases, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins, Guanine Nucleotide Dissociation Inhibitors
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