Source:http://linkedlifedata.com/resource/pubmed/id/11792712
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2002-3-18
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| pubmed:abstractText |
Conformational changes in integrins are important for efficient ligand binding during activation. We proposed that the I domain of the integrin lymphocyte function-associated antigen 1 (LFA-1) could exist in both open and closed conformations and generated constitutively activated LFA-1 by locking the I domain in the open conformation. Here we provide structural and biochemical evidence to validate conformational change in the I domain of LFA-1 upon activation. Two monoclonal antibodies to alpha(L), HI111 and CBR LFA-1/1, bind wild-type LFA-1 well, but their binding is significantly reduced when LFA-1 is locked in the open conformation. Furthermore, this reduction in monoclonal antibody binding also occurs when LFA-1 is activated by divalent cations. HI111 maps to the top region of the I domain that is close to the putative ligand-binding site surrounding the MIDAS (metal ion-dependent adhesion site). The epitope of CBR LFA-1/1 is at the C-terminal segment of the I domain that links to the beta-propeller, and undergoes a large movement between the open and closed conformations. Our data demonstrate that these two regions undergo significant conformational changes during LFA-1 activation and that the I domain of activated LFA-1 adopts a similar tertiary structure as the predicted locked open form.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Cations,
http://linkedlifedata.com/resource/pubmed/chemical/Dithiothreitol,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Function-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
22
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| pubmed:volume |
277
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
10638-41
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11792712-Animals,
pubmed-meshheading:11792712-Antibodies, Monoclonal,
pubmed-meshheading:11792712-Cations,
pubmed-meshheading:11792712-Cell Adhesion,
pubmed-meshheading:11792712-Cell Line,
pubmed-meshheading:11792712-Dithiothreitol,
pubmed-meshheading:11792712-Epitopes,
pubmed-meshheading:11792712-Humans,
pubmed-meshheading:11792712-K562 Cells,
pubmed-meshheading:11792712-Kinetics,
pubmed-meshheading:11792712-Ligands,
pubmed-meshheading:11792712-Lymphocyte Function-Associated Antigen-1,
pubmed-meshheading:11792712-Mice,
pubmed-meshheading:11792712-Models, Molecular,
pubmed-meshheading:11792712-Protein Binding,
pubmed-meshheading:11792712-Protein Conformation,
pubmed-meshheading:11792712-Protein Structure, Tertiary,
pubmed-meshheading:11792712-Recombinant Fusion Proteins,
pubmed-meshheading:11792712-Surface Plasmon Resonance
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| pubmed:year |
2002
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| pubmed:articleTitle |
Activation-induced conformational changes in the I domain region of lymphocyte function-associated antigen 1.
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| pubmed:affiliation |
Department of Pathology, Center for Blood Research and Harvard Medical School, Boston, Massachusetts 02115, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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