Linked Life Data

15557320

Source:http://linkedlifedata.com/resource/pubmed/id/15557320

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-2-7
pubmed:abstractText
The overall structure of integrins is that of a ligand-binding head connected to two long legs. The legs can exhibit a pronounced bend at the "knees," and it has been proposed that the legs undergo a dramatic straightening when integrins transit from a low affinity to a high affinity state. The knee region contains domains from both alpha and beta subunits, including the N-terminal plexin/semaphorin/integrin (PSI) domain of the beta subunit. The role played by the knee domains in the regulation of integrin-ligand binding is uncertain. Here we show that: (i) monoclonal antibodies (mAbs) N29 and 8E3 have epitopes in the beta(1) subunit PSI domain and stimulate ligand binding to alpha(5)beta(1); (ii) N29 and 8E3 cause long range conformational changes that alter the ligand binding activity of the head region; (iii) the stimulatory action of these mAbs is dependent on the calf-1 domain, which forms part of the alpha subunit knee; and (iv) the epitopes of 8E3 and N29 map close to the extreme N terminus of the PSI and are likely to lie on the side of this domain that faces the alpha subunit. Taken together, our data suggest that the binding of these mAbs results in a levering apart of the PSI and calf-1 domains, and thereby causes the alpha and beta subunit knees to separate. Several major inferences can be drawn from our findings. First, the PSI domain appears to form part of an interface with the alpha subunit that normally restrains the integrin in a bent state. Second, the PSI domain is important for the transduction of conformational changes from the knee to head. Third, unbending is likely to provide a general mechanism for control of integrin-ligand recognition.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4238-46
pubmed:dateRevised
2006-4-21
pubmed:meshHeading
pubmed-meshheading:15557320-Animals, pubmed-meshheading:15557320-Antibodies, Monoclonal, pubmed-meshheading:15557320-CHO Cells, pubmed-meshheading:15557320-Cell Adhesion Molecules, pubmed-meshheading:15557320-Cricetinae, pubmed-meshheading:15557320-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:15557320-Epitope Mapping, pubmed-meshheading:15557320-Epitopes, pubmed-meshheading:15557320-Genetic Vectors, pubmed-meshheading:15557320-Humans, pubmed-meshheading:15557320-Integrin alpha5beta1, pubmed-meshheading:15557320-Integrin beta Chains, pubmed-meshheading:15557320-Integrins, pubmed-meshheading:15557320-Ligands, pubmed-meshheading:15557320-Mutagenesis, Site-Directed, pubmed-meshheading:15557320-Nerve Tissue Proteins, pubmed-meshheading:15557320-Placenta, pubmed-meshheading:15557320-Protein Binding, pubmed-meshheading:15557320-Protein Conformation, pubmed-meshheading:15557320-Protein Structure, Tertiary, pubmed-meshheading:15557320-Recombinant Proteins, pubmed-meshheading:15557320-Semaphorins
pubmed:year
2005
pubmed:articleTitle
Evidence that monoclonal antibodies directed against the integrin beta subunit plexin/semaphorin/integrin domain stimulate function by inducing receptor extension.
pubmed:affiliation
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom. paul.mould@manchester.ac.uk
pubmed:publicationType
Journal Article