3O6L

Anti-Tat HIV 11H6H1 Fab' complexed with a 15-mer Tat peptide

Summary for 3O6L

• Entry DOI: 10.2210/pdb3o6l/pdb
• Related: 3O6K 3O6M
• Descriptor: 11H6H1 Fab' light chain, 11H6H1 Fab' heavy chain, Protein Tat 15-mer peptide, ... (4 entities in total)
• Functional Keywords: antigen-binding site, u-shaped groove, immune system, tat hiv
• Biological source: Mus musculus (mouse); More
• Cellular location: Host nucleus, host nucleolus (By similarity): Q98XH7
• Total number of polymer chains: 3
• Total formula weight: 49491.22

Authors

Serriere, J.,Gouet, P.,Guillon, C. (deposition date: 2010-07-29, release date: 2010-11-10, Last modification date: 2023-09-06)

Primary citation

Serriere, J.,Dugua, J.M.,Bossus, M.,Verrier, B.,Haser, R.,Gouet, P.,Guillon, C.
Fab'-induced folding of antigenic N-terminal peptides from intrinsically disordered HIV-1 Tat revealed by X-ray crystallography.
J.Mol.Biol., 405:33-42, 2011

PubMed Abstract: 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.

PubMed: 21035463
DOI: 10.1016/j.jmb.2010.10.033

Experimental method

X-RAY DIFFRACTION (2.1 Å)