HIV-1 Capsid Function Is Regulated by Dynamics: Quantitative Atomic-Resolution Insights by Integrating Magic-Angle-Spinning NMR, QM/MM, and MD.
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 deca...
| Publicado en: | Journal of the American Chemical Society Vol. 138; no. 42; pp. 14066 - 14076 |
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| Autores principales: | , , , , , , , , , , , , , , |
| Formato: | Artículo |
| Publicado: |
American Chemical Society
10/26/2016
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| Materias: | |
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=119462160&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 119462160 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 10/26/2016 vid: 138 iid: 42 pid: 997 pub: American Chemical Society artinfo: ui: 119462160 10.1021/jacs.6b08744 ppf: 14066 ppct: 10 formats: tig: atl: HIV-1 Capsid Function Is Regulated by Dynamics: Quantitative Atomic-Resolution Insights by Integrating Magic-Angle-Spinning NMR, QM/MM, and MD. aug: au: Huilan Zhang Guangjin Hou Manman Lu Polenova, Tatyana Jinwoo Ahn Byeon, In-Ja L. Gronenborn, Angela M. Langmead, Christopher J. Perilla, Juan R. Schulten, Klaus Ivan Hung Gor'kov, Peter L. Zhehong Gan Brey, William W. Case, David A. affil: Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States. Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine, 1051 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States. Department of Structural Biology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States. Computer Science Department, Carnegie Mellon University, Gates Hillman Center, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States. Department of Physics and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana—Champaign, Urbana, Illinois 61801, United States. National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida 32310, United States. Department of Chemistry and Chemical Biology, Rutgers University, 174 Frelinghuysen Road, Piscataway, New Jersey 08854-8087, United States. su: Capsids HIV Time-dependent density functional theory Nuclear magnetic resonance spectroscopy HIV protease inhibitors Peptides sug: subj: Capsids HIV Time-dependent density functional theory Nuclear magnetic resonance spectroscopy HIV protease inhibitors Peptides 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 N 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. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2016 holdings: @attributes: islocal: N |
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