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PDBsum entry 3o6m
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Immune system
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PDB id
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3o6m
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References listed in PDB file
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Key reference
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Title
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Fab'-Induced folding of antigenic n-Terminal peptides from intrinsically disordered HIV-1 tat revealed by X-Ray crystallography.
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Authors
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J.Serrière,
J.M.Dugua,
M.Bossus,
B.Verrier,
R.Haser,
P.Gouet,
C.Guillon.
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Ref.
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J Mol Biol, 2011,
405,
33-42.
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PubMed id
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Abstract
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Tat, the transcriptional activator protein of human immunodeficiency virus type
1 (HIV-1), is critical for viral replication and is a potential HIV-1 vaccine
candidate. This intrinsically disordered protein is present in the extracellular
medium and is involved in the pathogenicity of HIV through its interaction with
different cellular and viral biological partners. A monoclonal antibody termed
11H6H1, which is specific for the N-terminal region of Tat, was selected for a
functional and structural study of the HIV-1 Tat protein. The equilibrium
dissociation constants (K(d)) of Tat and Tat fragments complexed with 11H6H1
were estimated by competitive ELISA. Tat contains a single tryptophan residue,
Trp11, located in the N-terminal region. We show that the substitution of Trp11
by a phenylalanine completely abolishes the binding of 11H6H1, whereas the
transactivating activity of Tat is preserved. The epitope recognized by 11H6H1
was restricted to the 9-mer peptide P(6)KLEPWKHP(14) centered on Trp11. The
crystal structures of this 9-mer peptide and of an overlapping 15-mer peptide
were determined in complex with Fab' 11H6H1 at 2.4 Å and 2.1 Å resolution,
respectively. Tat is intrinsically disordered and can undergo induced folding
upon association with a biological partner. Our crystallographic study reveals
that the two Tat peptides, which are lodged in the U-shaped groove of the Fab'
antigen-binding site, adopt a standard type I β-turn conformation. The central
Trp11 that is critical for Fab' recognition is further stabilized by π-stacking
interactions. The structural and biological consequences of this induced folding
in HIV pathogenesis are discussed.
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Secondary reference #1
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Title
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Uv and X-Ray structural studies of a 101-Residue long tat protein from a HIV-1 primary isolate and of its mutated, Detoxified, Vaccine candidate.
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Authors
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M.Foucault,
K.Mayol,
V.Receveur-Bréchot,
M.C.Bussat,
C.Klinguer-Hamour,
B.Verrier,
A.Beck,
R.Haser,
P.Gouet,
C.Guillon.
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Ref.
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Proteins, 2010,
78,
1441-1456.
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PubMed id
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