3o6m | pdb_00003o6m
Anti-Tat HIV 11H6H1 Fab' complexed with a 9-mer Tat peptide
Structural highlights
Publication Abstract from PubMedTat, 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 A and 2.1 A 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 beta-turn conformation. The central Trp11 that is critical for Fab' recognition is further stabilized by pi-stacking interactions. The structural and biological consequences of this induced folding in HIV pathogenesis are discussed. Fab'-Induced Folding of Antigenic N-Terminal Peptides from Intrinsically Disordered HIV-1 Tat Revealed by X-ray Crystallography.,Serriere J, Dugua JM, Bossus M, Verrier B, Haser R, Gouet P, Guillon C J Mol Biol. 2010 Oct 28. PMID:21035463[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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