Dynamics of linker residues modulate the nucleic acid binding properties of the HIV-1 nucleocapsid protein zinc fingers
| Autor: | Xiaoqian Xu, Yves Mély, Nelly Morellet, Loussiné Zargarian, Olivier Mauffret, Carine Tisné, Philippe Fosse, Brigitte René, Pierre Barraud |
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| Přispěvatelé: | Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Paris Descartes - Paris 5 (UPD5) - Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Viral Diseases Biochemistry Nucleocapsids Physical Chemistry chemistry.chemical_compound Immunodeficiency Viruses [CHIM] Chemical Sciences Macromolecular Structure Analysis Medicine and Health Sciences Zinc finger 0303 health sciences Multidisciplinary Physics Protein dynamics 030302 biochemistry & molecular biology Magnetism Zinc Fingers Nucleocapsid Proteins Condensed Matter Physics 3. Good health Chemistry Infectious Diseases Medical Microbiology Viral Pathogens Physical Sciences Medicine Research Article Protein Structure Rotation Nuclear Magnetic Resonance Science Viral Structure Microbiology 03 medical and health sciences Virology [CHIM]Chemical Sciences [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Microbial Pathogens Molecular Biology 030304 developmental biology LIM domain Biology and Life Sciences Proteins Computational Biology HIV RNA Nucleic Acid Strand DNA Chemical Properties chemistry HIV-1 Nucleic acid Biophysics Linker |
| Zdroj: | PLoS ONE, Vol 9, Iss 7, p e102150 (2014) PLoS ONE PLoS ONE, Public Library of Science, 2013, 9 (7), pp.e102150 PLoS ONE, Public Library of Science, 2014, 9, ⟨10.1371/journal.pone.0102150⟩ |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0102150⟩ |
| Popis: | International audience; The HIV-1 nucleocapsid protein (NC) is a small basic protein containing two zinc fingers (ZF) separated by a short linker. It is involved in several steps of the replication cycle and acts as a nucleic acid chaperone protein in facilitating nucleic acid strand transfers occurring during reverse transcription. Recent analysis of three-dimensional structures of NC-nucleic acids complexes established a new property: the unpaired guanines targeted by NC are more often inserted in the C-terminal zinc finger (ZF2) than in the N-terminal zinc finger (ZF1). Although previous NMR dynamic studies were performed with NC, the dynamic behavior of the linker residues connecting the two ZF domains remains unclear. This prompted us to investigate the dynamic behavior of the linker residues. Here, we collected 15 N NMR relaxation data and used for the first time data at several fields to probe the protein dynamics. The analysis at two fields allows us to detect a slow motion occurring between the two domains around a hinge located in the linker at the G35 position. However, the amplitude of motion appears limited in our conditions. In addition, we showed that the neighboring linker residues R29, A30, P31, R32, K33 displayed restricted motion and numerous contacts with residues of ZF1. Our results are fully consistent with a model in which the ZF1-linker contacts prevent the ZF1 domain to interact with unpaired guanines, whereas the ZF2 domain is more accessible and competent to interact with unpaired guanines. In contrast, ZF1 with its large hydrophobic plateau is able to destabilize the double-stranded regions adjacent to the guanines bound by ZF2. The linker residues and the internal dynamics of NC regulate therefore the different functions of the two zinc fingers that are required for an optimal chaperone activity. |
| Databáze: | OpenAIRE |
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