NMR Observable-Based Structure Refinement of DAP12-NKG2C Activating Immunoreceptor Complex in Explicit Membranes
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Issue Date
2012-04-04Author
Cheng, Xi
Im, Wonpil
Publisher
Elsevier
Type
Article
Article Version
Scholarly/refereed, publisher version
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Show full item recordAbstract
NMR observables, such as NOE-based distance measurements, are increasingly being used to characterize membrane protein structures. However, challenges in membrane protein NMR studies often yield a relatively small number of such restraints that can create ambiguities in defining critical side chain-side chain interactions. In the recent solution NMR structure of the DAP12-NKG2C immunoreceptor transmembrane helix complex, five functionally required interfacial residues (two Asps and two Thrs in the DAP12 dimer and one Lys in NKG2C) display a surprising arrangement in which one Asp side chain faces the membrane hydrophobic core. To explore whether these side-chain interactions are energetically optimal, we used the published distance restraints for molecular dynamics simulations in explicit micelles and bilayers. The structures refined by this protocol are globally similar to the published structure, but the side chains of those five residues form a stable network of salt bridges and hydrogen bonds, leaving the Asp side chain shielded from the hydrophobic core, which is also consistent with available experimental observations. Moreover, the simulations show similar short-range interactions between the transmembrane complex and lipid/detergent molecules in micelles and bilayers, respectively. This study illustrates the efficacy of NMR membrane protein structure refinements in explicit membrane systems.
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This is the published version. Copyright 2012 by Elsevier.
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Citation
Cheng, Xi, and Wonpil Im. "NMR Observable-Based Structure Refinement of DAP12-NKG2C Activating Immunoreceptor Complex in Explicit Membranes." Biophysical Journal 102.7 (2012): L27-29. http://dx.doi.org/10.1016/j.bpj.2012.03.002.
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