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PDBsum entry 3mia
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Protein binding
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PDB id
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3mia
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Contents |
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325 a.a.
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247 a.a.
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48 a.a.
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References listed in PDB file
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Key reference
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Title
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Crystal structure of HIV-1 tat complexed with human p-Tefb.
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Authors
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T.H.Tahirov,
N.D.Babayeva,
K.Varzavand,
J.J.Cooper,
S.C.Sedore,
D.H.Price.
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Ref.
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Nature, 2010,
465,
747-751.
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PubMed id
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Abstract
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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.
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