Integrated Structural Biology for α-Helical Membrane Protein Structure Determination.

Xia Y, Fischer AW, Teixeira P, Weiner B, Meiler J
Structure. 2018 26 (4): 657-666.e2

PMID: 29526436 · PMCID: PMC5884713 · DOI:10.1016/j.str.2018.02.006

While great progress has been made, only 10% of the nearly 1,000 integral, α-helical, multi-span membrane protein families are represented by at least one experimentally determined structure in the PDB. Previously, we developed the algorithm BCL::MP-Fold, which samples the large conformational space of membrane proteins de novo by assembling predicted secondary structure elements guided by knowledge-based potentials. Here, we present a case study of rhodopsin fold determination by integrating sparse and/or low-resolution restraints from multiple experimental techniques including electron microscopy, electron paramagnetic resonance spectroscopy, and nuclear magnetic resonance spectroscopy. Simultaneous incorporation of orthogonal experimental restraints not only significantly improved the sampling accuracy but also allowed identification of the correct fold, which is demonstrated by a protein size-normalized transmembrane root-mean-square deviation as low as 1.2 Å. The protocol developed in this case study can be used for the determination of unknown membrane protein folds when limited experimental restraints are available.

Copyright © 2018 Elsevier Ltd. All rights reserved.

MeSH Terms (15)

Algorithms Binding Sites Electron Spin Resonance Spectroscopy Humans Membrane Proteins Microscopy, Electron Models, Molecular Monte Carlo Method Nuclear Magnetic Resonance, Biomolecular Protein Binding Protein Conformation, alpha-Helical Protein Folding Protein Interaction Domains and Motifs Rhodopsin Thermodynamics

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