3MI9

Crystal structure of HIV-1 Tat complexed with human P-TEFb

3MI9 の概要

• エントリーDOI: 10.2210/pdb3mi9/pdb
• 関連するPDBエントリー: 3MIA
• 分子名称: Cell division protein kinase 9, Cyclin-T1, Protein Tat, ... (5 entities in total)
• 機能のキーワード: p-tefb, tat, hiv-1, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P50750 O60563; Host nucleus, host nucleolus: P04608
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 81548.62

構造登録者

Tahirov, T.H.,Babayeva, N.D.,Varzavand, K.,Cooper, J.J.,Sedore, S.C.,Price, D.H. (登録日: 2010-04-09, 公開日: 2010-06-09, 最終更新日: 2024-11-27)

主引用文献

Tahirov, T.H.,Babayeva, N.D.,Varzavand, K.,Cooper, J.J.,Sedore, S.C.,Price, D.H.
Crystal structure of HIV-1 Tat complexed with human P-TEFb.
Nature, 465:747-751, 2010

PubMed Abstract: Regulation of the expression of the human immunodeficiency virus (HIV) genome is accomplished in large part by controlling transcription elongation. The viral protein Tat hijacks the host cell's RNA polymerase II elongation control machinery through interaction with the positive transcription elongation factor, P-TEFb, and directs the factor to promote productive elongation of HIV mRNA. Here we describe the crystal structure of the Tat.P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1). Tat adopts a structure complementary to the surface of P-TEFb and makes extensive contacts, mainly with the cyclin T1 subunit of P-TEFb, but also with the T-loop of the Cdk9 subunit. The structure provides a plausible explanation for the tolerance of Tat to sequence variations at certain sites. Importantly, Tat induces significant conformational changes in P-TEFb. This finding lays a foundation for the design of compounds that would specifically inhibit the Tat.P-TEFb complex and block HIV replication.

PubMed: 20535204
DOI: 10.1038/nature09131

実験手法

X-RAY DIFFRACTION (2.1 Å)