TY - JOUR
T1 - HIV-1 Capsid Function Is Regulated by Dynamics
T2 - Quantitative Atomic-Resolution Insights by Integrating Magic-Angle-Spinning NMR, QM/MM, and MD
AU - Zhang, Huilan
AU - Hou, Guangjin
AU - Lu, Manman
AU - Ahn, Jinwoo
AU - Byeon, In Ja L.
AU - Langmead, Christopher J.
AU - Perilla, Juan R.
AU - Hung, Ivan
AU - Gor'Kov, Peter L.
AU - Gan, Zhehong
AU - Brey, William W.
AU - Case, David A.
AU - Schulten, Klaus
AU - Gronenborn, Angela M.
AU - Polenova, Tatyana
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/10/26
Y1 - 2016/10/26
N2 - HIV-1 CA capsid protein possesses intrinsic conformational flexibility, which is essential for its assembly into conical capsids and interactions with host factors. CA is dynamic in the assembled capsid, and residues in functionally important regions of the protein undergo motions spanning many decades of time scales. Chemical shift anisotropy (CSA) tensors, recorded in magic-angle-spinning NMR experiments, provide direct residue-specific probes of motions on nano- to microsecond time scales. We combined NMR, MD, and density-functional-theory calculations, to gain quantitative understanding of internal backbone dynamics in CA assemblies, and we found that the dynamically averaged 15N CSA tensors calculated by this joined protocol are in remarkable agreement with experiment. Thus, quantitative atomic-level understanding of the relationships between CSA tensors, local backbone structure, and motions in CA assemblies is achieved, demonstrating the power of integrating NMR experimental data and theory for characterizing atomic-resolution dynamics in biological systems.
AB - HIV-1 CA capsid protein possesses intrinsic conformational flexibility, which is essential for its assembly into conical capsids and interactions with host factors. CA is dynamic in the assembled capsid, and residues in functionally important regions of the protein undergo motions spanning many decades of time scales. Chemical shift anisotropy (CSA) tensors, recorded in magic-angle-spinning NMR experiments, provide direct residue-specific probes of motions on nano- to microsecond time scales. We combined NMR, MD, and density-functional-theory calculations, to gain quantitative understanding of internal backbone dynamics in CA assemblies, and we found that the dynamically averaged 15N CSA tensors calculated by this joined protocol are in remarkable agreement with experiment. Thus, quantitative atomic-level understanding of the relationships between CSA tensors, local backbone structure, and motions in CA assemblies is achieved, demonstrating the power of integrating NMR experimental data and theory for characterizing atomic-resolution dynamics in biological systems.
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U2 - 10.1021/jacs.6b08744
DO - 10.1021/jacs.6b08744
M3 - Article
AN - SCOPUS:84992688629
SN - 0002-7863
VL - 138
SP - 14066
EP - 14075
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 42
ER -