5SVZ

HIV-1 Tat NLS in complex with importin alpha

5SVZ の概要

• エントリーDOI: 10.2210/pdb5svz/pdb
• 分子名称: Importin subunit alpha-1, Tat (3 entities in total)
• 機能のキーワード: hiv-1, tat, importin alpha, virus, complex, transport protein-viral protein complex, transport protein/viral protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• 細胞内の位置: Cytoplasm : P52293
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57170.69

構造登録者

Smith, K.M.,Himiari, Z.,Forwood, J.K. (登録日: 2016-08-08, 公開日: 2016-08-31, 最終更新日: 2023-10-04)

主引用文献

Smith, K.M.,Himiari, Z.,Tsimbalyuk, S.,Forwood, J.K.
Structural Basis for Importin-alpha Binding of the Human Immunodeficiency Virus Tat.
Sci Rep, 7:1650-1650, 2017

PubMed Abstract: HIV-1 has caused 35 million deaths globally, and approximately the same number is currently living with HIV-1. The trans-activator of transcription (Tat) protein of HIV-1 plays an important regulatory function in the virus life cycle, responsible for regulating the reverse transcription of the viral genome RNA. Tat is found in the nucleus of infected cells, but can also invade uninfected neighbouring cells. Regions within Tat responsible for these cellular localisations are overlapping and include a nuclear localisation signal (NLS) spanning GRKKRR, and a cell penetrating peptide (CPP) signal spanning GRKKRRQRRRAPQN. However, the mechanism by which this NLS/CPP region mediates interaction with the nuclear import receptors remains to be resolved structurally. Here, we establish that the HIV-1 Tat:NLS/CPP is able to form a stable and direct interaction with the classical nuclear import receptor importin-α and using x-ray crystallography, we have determined the molecular interface and binding determinants to a resolution of 2.0 Å. We show for the first time that the interface is the same as host factors such as Ku70 and Ku80, rather than other virus proteins such as Ebola VP24 that bind on the outer surface of importin-α.

PubMed: 28490747
DOI: 10.1038/s41598-017-01853-7

実験手法

X-RAY DIFFRACTION (2 Å)