HIV-1 Capsid Function Is Regulated by Dynamics: Quantitative Atomic-Resolution Insights by Integrating Magic-Angle-Spinning NMR, QM/MM, and MD

Huilan Zhang, Guangjin Hou, Manman Lu, Jinwoo Ahn, In Ja L. Byeon, Christopher J. Langmead, Juan R. Perilla, Ivan Hung, Peter L. Gor'Kov, Zhehong Gan, William W. Brey, David A. Case, Klaus Schulten, Angela M. Gronenborn, Tatyana Polenova

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)14066-14075
Number of pages10
JournalJournal of the American Chemical Society
Volume138
Issue number42
DOIs
StatePublished - Oct 26 2016

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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