5SVZ

HIV-1 Tat NLS in complex with importin alpha


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.175 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural Basis for Importin-alpha Binding of the Human Immunodeficiency Virus Tat.

Smith, K.M.Himiari, Z.Tsimbalyuk, S.Forwood, J.K.

(2017) Sci Rep 7: 1650-1650

  • DOI: https://doi.org/10.1038/s41598-017-01853-7
  • Primary Citation of Related Structures:  
    5SVZ

  • 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 48 GRKKRR, and a cell penetrating peptide (CPP) signal spanning 48 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.


  • Organizational Affiliation

    Charles Sturt University, School of Biomedical Sciences, Wagga Wagga, 2678, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Importin subunit alpha-1510Mus musculusMutation(s): 0 
Gene Names: Kpna2Rch1
UniProt & NIH Common Fund Data Resources
Find proteins for P52293 (Mus musculus)
Explore P52293 
Go to UniProtKB:  P52293
IMPC:  MGI:103561
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP52293
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Tat15Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for P04326 (Human immunodeficiency virus type 1 group M subtype B (isolate PCV12))
Explore P04326 
Go to UniProtKB:  P04326
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04326
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.175 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79α = 90
b = 89.831β = 90
c = 99.46γ = 90
Software Package:
Software NamePurpose
Aimlessdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
iMOSFLMdata reduction
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-08-31
    Type: Initial release
  • Version 1.1: 2017-05-31
    Changes: Database references
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Refinement description