ArticleProceedings of the National Academy of Sciences of the United States of America2012
Revealing conformational substates of lipidated N-Ras protein by pressure modulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- A molten globule ensemble primes Arf1-GDP for the nucleotide switch.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- From disorder comes function: Regulation of small GTPase function by intrinsically disordered lipidated membrane anchor.Current opinion in structural biology · 2024Review
- GTP-Bound N-Ras Conformational States and Substates Are Modulated by Membrane and Point Mutation.International journal of molecular sciences · 2024Article
- Review
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- Article
- Lipid Profiles of RAS Nanoclusters Regulate RAS Function.Biomolecules · 2021Review
- Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid Membranes.International journal of molecular sciences · 2021Article
- Approaches to inhibiting oncogenic K-Ras.Small GTPases · 2021Review
- The Ins and Outs of RAS Effector Complexes.Biomolecules · 2021Review
- Investigating the influence of physiologically relevant hydrostatic pressure on CHO cell batch culture.Scientific reports · 2021Article
- Influence of Cholesterol on the Orientation of the Farnesylated GTP-Bound KRas-4B Binding with Anionic Model Membranes.Membranes · 2020Article
- Mechanisms of Ras Membrane Organization and Signaling: Ras Rocks Again.Biomolecules · 2020Review
- Pressure Sensitivity of SynGAP/PSD-95 Condensates as a Model for Postsynaptic Densities and Its Biophysical and Neurological Ramifications.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Membrane-Bound Ras as a Conformational Clock.Biophysical journal · 2020Article
- Dual role of a GTPase conformational switch for membrane fusion by mitofusin ubiquitylation.Life science alliance · 2020Article
- Probing the Conformational and Energy Landscapes of KRAS Membrane Orientation.The journal of physical chemistry. B · 2019Article
- Membrane Dynamics in Health and Disease: Impact on Cellular Signalling.The Journal of membrane biology · 2019Review
- Three distinct regions of cRaf kinase domain interact with membrane.Scientific reports · 2019Article
- RAS variant signalling.Biochemical Society transactions · 2018Review
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6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Regulation of protein function is often linked to a conformational switch triggered by chemical or physical signals. To evaluate such conformational changes and to elucidate the underlying molecular mechanisms of subsequent protein function, experimental identification of conformational substates and characterization of conformational equilibria are mandatory. We apply pressure modulation in combination with FTIR spectroscopy to reveal equilibria between spectroscopically resolved substates of the lipidated signaling protein N-Ras. Pressure has the advantage that its thermodynamic conjugate is volume, a parameter that is directly related to structure. The conformational dynamics of N-Ras in its different nucleotide binding states in the absence and presence of a model biomembrane was probed by pressure perturbation. We show that not only nucleotide binding but also the presence of the membrane has a drastic effect on the conformational dynamics and selection of conformational substates of the protein, and a new substate appearing upon membrane binding could be uncovered. Population of this new substate is accompanied by structural reorientations of the G domain, as also indicated by complementary ATR-FTIR and IRRAS measurements. These findings thus illustrate that the membrane controls signaling conformations by acting as an effective interaction partner, which has consequences for the G-domain orientation of membrane-associated N-Ras, which in turn is known to be critical for its effector and modulator interactions. Finally, these results provide insights into the influence of pressure on Ras-controlled signaling events in organisms living under extreme environmental conditions as they are encountered in the deep sea where pressures reach the kbar range.
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