5I1R

Quantitative characterization of configurational space sampled by HIV-1 nucleocapsid using solution NMR and X-ray scattering

5I1R の概要

• エントリーDOI: 10.2210/pdb5i1r/pdb
• NMR情報: BMRB: 30008
• 分子名称: Nucleocapsid protein p7, ZINC ION (2 entities in total)
• 機能のキーワード: viral protein
• 由来する生物種: Human immunodeficiency virus type 1 (HXB2 ISOLATE) (HIV-1)
• 細胞内の位置: Gag polyprotein: Host cell membrane; Lipid- anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion : P04591
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6573.34

構造登録者

Deshmukh, L.,Schwieters, C.D.,Grishaev, A.,Clore, G.M. (登録日: 2016-02-05, 公開日: 2016-03-30, 最終更新日: 2024-05-15)

主引用文献

Deshmukh, L.,Schwieters, C.D.,Grishaev, A.,Clore, G.M.
Quantitative Characterization of Configurational Space Sampled by HIV-1 Nucleocapsid Using Solution NMR, X-ray Scattering and Protein Engineering.
Chemphyschem, 17:1548-1552, 2016

PubMed Abstract: Nucleic-acid-related events in the HIV-1 replication cycle are mediated by nucleocapsid, a small protein comprising two zinc knuckles connected by a short flexible linker and flanked by disordered termini. Combining experimental NMR residual dipolar couplings, solution X-ray scattering and protein engineering with ensemble simulated annealing, we obtain a quantitative description of the configurational space sampled by the two zinc knuckles, the linker and disordered termini in the absence of nucleic acids. We first compute the conformational ensemble (with an optimal size of three members) of an engineered nucleocapsid construct lacking the N- and C-termini that satisfies the experimental restraints, and then validate this ensemble, as well as characterize the disordered termini, using the experimental data from the full-length nucleocapsid construct. The experimental and computational strategy is generally applicable to multidomain proteins. Differential flexibility within the linker results in asymmetric motion of the zinc knuckles which may explain their functionally distinct roles despite high sequence identity. One of the configurations (populated at a level of ≈40 %) closely resembles that observed in various ligand-bound forms, providing evidence for conformational selection and a mechanistic link between protein dynamics and function.

PubMed: 26946052
DOI: 10.1002/cphc.201600212

実験手法

SOLUTION NMR
SOLUTION SCATTERING