Linked Life Data

7616571

Source:http://linkedlifedata.com/resource/pubmed/id/7616571

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-8-24
pubmed:abstractText
The conformational switch at the principle CD4-binding domain of gp120 from HIV1 exhibits a highly cooperative folding transition from beta-sheet to helix triggered within a very narrow range of solvent polarity. The physical basis of this folding behaviour is of interest because it is unusual and because it is closely connected with biological function, i.e. binding to the CD4 receptor. Previous work revealed two primary structural elements, an N-terminal LPCR tetrad and a tryptophan residue eight residues C-terminal to this, that were essential for the helical and for the beta-sheet conformation, respectively. Attempts to construct synthetic "switch" domains using the characteristics so far identified produce peptides undergoing the transition at much higher polarity and involving fewer residues than the natural domain, in essence a lower stability of the beta-fold to apolar conditions. Introduction of a tryptophan residue reduced at the C(2)-C(3) linkage demonstrates clearly that the aromatic system of the tryptophan residue is central to beta-sheet stabilization. Residues with side-chains that might participate in electrostatic or aromatic interactions with the pi-electron system of Trp were sequentially altered to alanine. The results indicate that the "switch" properties of the CD4-binding domain arise from a poised tension between multiple interactions with the Trp aromatic ring stabilizing the beta-structure and the tendency of the LPCR tetrad to act as a template for a helical fold. Under polar conditions the former dominate. Lowering the polarity alters this both by weakening the aromatic interactions and by simultaneously increasing the helical propensities of the isoleucine and valine side-chains. Tryptophan seems uniquely suited to act as a polarity-sensitive conformational sensor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
250
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
507-13
pubmed:dateRevised
2001-11-13
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Investigation of the structural components governing the polarity-dependent refolding of a CD4-binding peptide from gp120.
pubmed:affiliation
Department of Pathochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany.
pubmed:publicationType
Journal Article