5SVZ

HIV-1 Tat NLS in complex with importin alpha

Summary for 5SVZ

• Entry DOI: 10.2210/pdb5svz/pdb
• Descriptor: Importin subunit alpha-1, Tat (3 entities in total)
• Functional Keywords: hiv-1, tat, importin alpha, virus, complex, transport protein-viral protein complex, transport protein/viral protein
• Biological source: Mus musculus (Mouse); More
• Cellular location: Cytoplasm : P52293
• Total number of polymer chains: 2
• Total formula weight: 57170.69

Authors

Smith, K.M.,Himiari, Z.,Forwood, J.K. (deposition date: 2016-08-08, release date: 2016-08-31, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)