5J1O

Excited state (Bound-like) sampled during RDC restrained Replica-averaged Metadynamics (RAM) simulations of the HIV-1 TAR complexed with cyclic peptide mimetic of Tat

5J1O の概要

• エントリーDOI: 10.2210/pdb5j1o/pdb
• NMR情報: BMRB: 30049
• 分子名称: Cyclic peptide mimetic of Tat, Apical region (29mer) of the HIV-1 TAR element (2 entities in total)
• 機能のキーワード: tar:tat complex, ram simulations, residual dipolar couplings, excited state, viral protein
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 11075.74

構造登録者

Borkar, A.N.,Bardaro, M.F.,Varani, G.,Vendruscolo, M. (登録日: 2016-03-29, 公開日: 2016-06-08, 最終更新日: 2024-10-23)

主引用文献

Borkar, A.N.,Bardaro, M.F.,Camilloni, C.,Aprile, F.A.,Varani, G.,Vendruscolo, M.
Structure of a low-population binding intermediate in protein-RNA recognition.
Proc.Natl.Acad.Sci.USA, 113:7171-7176, 2016

PubMed Abstract: The interaction of the HIV-1 protein transactivator of transcription (Tat) and its cognate transactivation response element (TAR) RNA transactivates viral transcription and represents a paradigm for the widespread occurrence of conformational rearrangements in protein-RNA recognition. Although the structures of free and bound forms of TAR are well characterized, the conformations of the intermediates in the binding process are still unknown. By determining the free energy landscape of the complex using NMR residual dipolar couplings in replica-averaged metadynamics simulations, we observe two low-population intermediates. We then rationally design two mutants, one in the protein and another in the RNA, that weaken specific nonnative interactions that stabilize one of the intermediates. By using surface plasmon resonance, we show that these mutations lower the release rate of Tat, as predicted. These results identify the structure of an intermediate for RNA-protein binding and illustrate a general strategy to achieve this goal with high resolution.

PubMed: 27286828
DOI: 10.1073/pnas.1521349113

実験手法

SOLUTION NMR