Year: 2014
Type: article
Abstract: The Ras family of small membrane-associated GTP-ases are important components in many different cell signalling cascades. They are thought to cluster on the cell membrane through association with cholesterol-rich nanodomains. This process remains poorly understood. Here we test the effect of adding multiple copies of NRas, one of the canonical Ras proteins, to a three-component lipid bilayer that rapidly undergoes spinodal decomposition (i.e. unmixing), thereby creating ordered and disordered phases. Coarse-grained molecular dynamics simulations of a large bilayer containing 6000 lipids, with and without protein, are compared. NRas preferentially localises to the interface between the domains and slows the rate at which the domains grow. We infer that this doubly-lipidated cell signalling protein is reducing the line tension between the ordered and disordered regions. This analysis is facilitated by our use of techniques borrowed from image-processing. The conclusions above are contingent upon several assumptions, including the use of a model lipid with doubly unsaturated tails and the limited structural data available for the C-terminus of NRas, which is where the lipid anchors are found.
Source: Faraday Discussions
DOI: 10.1039/c3fd00131h
Institution: University of Oxford
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,373
Awards: G1015763213, G1502084111, Computational tools for enzyme engineering: bridging the gap between enzymologists and expert simulation, G1592560434, G1717999737, G1778333383, BrisSynBio: Bristol Centre for Synthetic Biology, CCP-BioSim: Biomolecular simulation at the life sciences interface, Inquire: Software for real-time analysis of binding, G271256356, G3583580618, G3889144934, Multi-Scale Integrative Modelling of Signalling at Membranes., CCP-BioSim: Biomolecular simulation at the life sciences interface, G4799187780, G504678512, Combined experimental and computational investigations of a nucleophilic displacement reaction with a hydride leaving group, Adaptive Multi-Resolution Massively-Multicore Hybrid Dynamics, Combined quantum mechanics/molecular mechanics (QM/MM) Monte Carlo free energy simulations: a feasibility study, OMSys: Towards a systems model of a bacterial outer membrane, G7080100828, G712558274, Crowding and Complexity: Simulation Studies of Biologically Realistic Membrane Models, Multiscale Ensemble Computing for Modelling Biological Catalysts, Computational biochemistry: predictive modelling for biology and medicine, G7814653466, G783393384, G8080688728, G8294306494, MemProtMD: A resource for membrane proteins, The UK High-End Computing Consortium for Biomolecular Simulation, G8858561294, G8947107902
OpenAlex ID: W1997601905