PDBsum entry 3o6m

Immune system

PDB id: 3o6m

Contents

Protein chains

216 a.a. *

218 a.a. *

Ligands

PRO-LYS-LEU-GLU-PRO-TRP-LYS-HIS-PRO

Waters ×101

* Residue conservation analysis

PDB id:

3o6m

Name:

Immune system

Title:

Anti-tat HIV 11h6h1 fab' complexed with a 9-mer tat peptide

Structure:

11h6h1 fab' light chain. Chain: l. 11h6h1 fab' heavy chain. Chain: h. Protein tat 9-mer peptide. Chain: c. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Strain: balb/c. Synthetic: yes. Other_details: the peptide was chemically synthesized'

Resolution:

2.40Å R-factor: 0.215 R-free: 0.290

Authors:

J.Serriere,P.Gouet,C.Guillon

Key ref:

J.Serrière et al. (2011). 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. PubMed id: 21035463

Date:

29-Jul-10 Release date: 10-Nov-10

Protein chain

No UniProt id for this chain

Struc: 216 a.a.

Protein chain

No UniProt id for this chain

Struc: 218 a.a.

J Mol Biol 405:33-42 (2011)

PubMed id: 21035463

Fab'-induced folding of antigenic N-terminal peptides from intrinsically disordered HIV-1 Tat revealed by X-ray crystallography.

J.Serrière, J.M.Dugua, M.Bossus, B.Verrier, R.Haser, P.Gouet, C.Guillon.

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.