Accurate Determination of Conformational Transitions in Oligomeric Membrane Proteins

Máximo Sanz-Hernández, Vitaly V. Vostrikov, Gianluigi Veglia, Alfonso De Simone

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


The structural dynamics governing collective motions in oligomeric membrane proteins play key roles in vital biomolecular processes at cellular membranes. In this study, we present a structural refinement approach that combines solid-state NMR experiments and molecular simulations to accurately describe concerted conformational transitions identifying the overall structural, dynamical, and topological states of oligomeric membrane proteins. The accuracy of the structural ensembles generated with this method is shown to reach the statistical error limit, and is further demonstrated by correctly reproducing orthogonal NMR data. We demonstrate the accuracy of this approach by characterising the pentameric state of phospholamban, a key player in the regulation of calcium uptake in the sarcoplasmic reticulum, and by probing its dynamical activation upon phosphorylation. Our results underline the importance of using an ensemble approach to characterise the conformational transitions that are often responsible for the biological function of oligomeric membrane protein states.

Original languageEnglish (US)
Article number23063
JournalScientific reports
StatePublished - Mar 15 2016

Bibliographical note

Funding Information:
This research was supported by the British Hearth Foundation (PG/14/93/31237 to A.D.), UK Engineering and Physical Research Council (EP1579441 to M.S.) and the National Institute of Health (GM64742 to G.V. and 5T32AR007612-14 to V.V.). The Imperial College High Performance Computing Service provided computational resources.


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