3MIA

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.219 

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Literature

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

Tahirov, T.H.Babayeva, N.D.Varzavand, K.Cooper, J.J.Sedore, S.C.Price, D.H.

(2010) Nature 465: 747-751

  • DOI: https://doi.org/10.1038/nature09131
  • Primary Citation of Related Structures:  
    3MI9, 3MIA

  • 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.


  • Organizational Affiliation

    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-7696, USA. ttahirov@unmc.edu


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division protein kinase 9351Homo sapiensMutation(s): 0 
Gene Names: CDC2L4CDK9
EC: 2.7.11.22 (PDB Primary Data), 2.7.11.23 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P50750 (Homo sapiens)
Explore P50750 
Go to UniProtKB:  P50750
PHAROS:  P50750
GTEx:  ENSG00000136807 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP50750
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclin-T1266Homo sapiensMutation(s): 0 
Gene Names: CCNT1Cyclin T1
UniProt & NIH Common Fund Data Resources
Find proteins for O60563 (Homo sapiens)
Explore O60563 
Go to UniProtKB:  O60563
PHAROS:  O60563
GTEx:  ENSG00000129315 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO60563
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Protein Tat86HIV-1 M:B_HXB2RMutation(s): 1 
Gene Names: tat
UniProt
Find proteins for P04608 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04608 
Go to UniProtKB:  P04608
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04608
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
TPO
Query on TPO
A
L-PEPTIDE LINKINGC4 H10 N O6 PTHR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.219 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 134.286α = 90
b = 134.286β = 90
c = 97.185γ = 120
Software Package:
Software NamePurpose
ADSCdata collection
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-06-09
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description