PDBsum entry 5svz

Transport protein/viral protein

PDB id: 5svz

Contents

Protein chain

426 a.a.

Ligands

GLY-ARG-LYS-LYS-ARG-ARG-GLN-ARG

Waters ×314

References listed in PDB file

Key reference

• Title: Structural basis for importin-α Binding of the human immunodeficiency virus tat.
• Authors: K.M.Smith, Z.Himiari, S.Tsimbalyuk, J.K.Forwood.
• Ref.: Sci Rep, 2017, 7, 1650.
• PubMed id: 28490747

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) spanning⁴⁸GRKKRR, and a cell penetrating peptide (CPP) signal spanning⁴⁸GRKKRRQRRRAPQN. 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.