2016
DOI: 10.1021/acs.chemrev.5b00542
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Abstract: Ras proteins are classical members of small GTPases that function as molecular switches by alternating between inactive GDP-bound and active GTP-bound states. Ras activation is regulated by guanine nucleotide exchange factors that catalyze the exchange of GDP by GTP, and inactivation is terminated by GTPase-activating proteins that accelerate the intrinsic GTP hydrolysis rate by orders of magnitude. In this review, we focus on data that have accumulated over the past few years pertaining to the conformational … Show more

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Cited by 297 publications
(331 citation statements)
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References 462 publications
(783 reference statements)
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“…Similar allosteric modulation of receptor function has been demonstrated in diverse membrane protein families, including G-protein-coupled receptors, receptor tyrosine kinases, and proton channels (37,39,(41)(42)(43)(44), as well as soluble cytoplasmic proteins containing lipid-targeting domains (45,46). Lipids impact the structure and function of membrane-embedded or membrane-associated proteins either through bulk effects mediated by the phospholipid bilayer or through binding of lipid molecules at specific sites (40,(47)(48)(49)(50).…”
Section: Discussion Lipids As Allosteric Modulators Of Membrane Protementioning
confidence: 67%
“…Similar allosteric modulation of receptor function has been demonstrated in diverse membrane protein families, including G-protein-coupled receptors, receptor tyrosine kinases, and proton channels (37,39,(41)(42)(43)(44), as well as soluble cytoplasmic proteins containing lipid-targeting domains (45,46). Lipids impact the structure and function of membrane-embedded or membrane-associated proteins either through bulk effects mediated by the phospholipid bilayer or through binding of lipid molecules at specific sites (40,(47)(48)(49)(50).…”
Section: Discussion Lipids As Allosteric Modulators Of Membrane Protementioning
confidence: 67%
“…A similar interface was proposed for K-Ras (Spencer-Smith et al, 2016;Prakash et al, 2017). Stephen et al, 2014;Chen et al, 2016;Lu et al, 2016), and elucidating the dimer interface at atomic detail will facilitate therapeutic approaches that modulate this interaction.…”
Section: Membrane Binding Of Rasmentioning
confidence: 69%
“…The overall structure of and common motifs present in small and heterotrimeric GTPases have been previously discussed in several excellent reviews (Hamm, 1998;Vetter and Wittinghofer, 2001;Wennerberg et al, 2005;Wittinghofer and Vetter, 2011;Ligeti et al, 2012;Cherfils and Zeghouf, 2013;Wittinghofer, 2014a,b;Carvalho et al, 2015;Lu et al, 2016;Mishra and Lambright, 2016;Sprang, 2016;Syrovatkina et al, 2016). Here, we will focus mainly on the results obtained from the orchestration of timeresolved Fourier transform infrared (FTIR) differencespectroscopy experiments and biomolecular simulations.…”
Section: Introduction: Small and Heterotrimeric Gtpasesmentioning
confidence: 99%
“…To perform its cellular roles, it switches between its inactive GDP-bound and active GTP-bound states 8,9 . Only active K-Ras (K-Ras-GTP) can bind and activate its downstream effector proteins 10 . Active K-Ras catalyzes GTP hydrolysis to become inactive (K-Ras-GDP).…”
Section: Introductionmentioning
confidence: 99%
“…However, certain mutations in K-Ras impair its intrinsic GTPase function and GAP binding and thereby GTP hydrolysis. Unable to switch to its GDP-bound inactive state, mutant K-Ras remains continuously active, causing prolonged activation of downstream pathways associated with oncogenic cell growth 10,[13][14][15] .…”
Section: Introductionmentioning
confidence: 99%