Linked Life Data

21035463

Source:http://linkedlifedata.com/resource/pubmed/id/21035463

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-21
pubmed:databankReference
pubmed:abstractText
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 ?-turn conformation. The central Trp11 that is critical for Fab' recognition is further stabilized by ?-stacking interactions. The structural and biological consequences of this induced folding in HIV pathogenesis are discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
405
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33-42
pubmed:meshHeading
pubmed-meshheading:21035463-Amino Acid Sequence, pubmed-meshheading:21035463-Amino Acid Substitution, pubmed-meshheading:21035463-Antibodies, Monoclonal, pubmed-meshheading:21035463-Antigens, Viral, pubmed-meshheading:21035463-Crystallography, X-Ray, pubmed-meshheading:21035463-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:21035463-Epitope Mapping, pubmed-meshheading:21035463-Epitopes, pubmed-meshheading:21035463-HIV Antibodies, pubmed-meshheading:21035463-HIV-1, pubmed-meshheading:21035463-Immunoglobulin Fab Fragments, pubmed-meshheading:21035463-Models, Molecular, pubmed-meshheading:21035463-Molecular Sequence Data, pubmed-meshheading:21035463-Mutagenesis, Site-Directed, pubmed-meshheading:21035463-Protein Binding, pubmed-meshheading:21035463-Protein Folding, pubmed-meshheading:21035463-Protein Structure, Tertiary, pubmed-meshheading:21035463-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2011
pubmed:articleTitle
Fab'-induced folding of antigenic N-terminal peptides from intrinsically disordered HIV-1 Tat revealed by X-ray crystallography.
pubmed:affiliation
Université de Lyon, IFR128 BioSciences Gerland-Lyon Sud, 7 Passage du Vercors, France.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't