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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2000-3-23
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pubmed:databankReference |
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pubmed:abstractText |
A key step in the activation of heterodimeric integrin adhesion receptors is the transmission of an agonist-induced cellular signal from the short alpha- and/or beta-cytoplasmic tails to the extracellular domains of the receptor. The structural details of how the cytoplasmic tails mediate such an inside-out signaling process remain unclear. We report herein the NMR structures of a membrane-anchored cytoplasmic tail of the alpha(IIb)-subunit and of a mutant alpha(IIb)-cytoplasmic tail that renders platelet integrin alpha(IIb)beta(3) constitutively active. The structure of the wild-type alpha(IIb)-cytoplasmic tail reveals a "closed" conformation where the highly conserved N-terminal membrane-proximal region forms an alpha-helix followed by a turn, and the acidic C-terminal loop interacts with the N-terminal helix. The structure of the active mutant is significantly different, having an "open" conformation where the interactions between the N-terminal helix and C-terminal region are abolished. Consistent with these structural differences, the two peptides differ in function: the wild-type peptide suppressed alpha(IIb)beta(3) activation, whereas the mutant peptide did not. These results provide an atomic explanation for extensive biochemical/mutational data and support a conformation-based "on/off switch" model for integrin activation.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-10212286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-10334926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-10358085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-10481014,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-1555235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-1948065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-2002847,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-2018974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-2738096,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-2938015,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-7510712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-7516703,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-7830597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-7918977,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-8520220,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-8626385,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-8636068,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-8876221,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-9030514,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-9077520,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-9082985,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-9425095,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-9685382,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-9691283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-9731063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10677482-9865695
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1450-5
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10677482-Amino Acid Sequence,
pubmed-meshheading:10677482-Antigens, CD18,
pubmed-meshheading:10677482-Blood Platelets,
pubmed-meshheading:10677482-Circular Dichroism,
pubmed-meshheading:10677482-Cytoplasm,
pubmed-meshheading:10677482-Fibrinogen,
pubmed-meshheading:10677482-Humans,
pubmed-meshheading:10677482-Magnetic Resonance Spectroscopy,
pubmed-meshheading:10677482-Models, Molecular,
pubmed-meshheading:10677482-Molecular Sequence Data,
pubmed-meshheading:10677482-Mutation,
pubmed-meshheading:10677482-Platelet Activation,
pubmed-meshheading:10677482-Platelet Glycoprotein GPIIb-IIIa Complex,
pubmed-meshheading:10677482-Protein Binding,
pubmed-meshheading:10677482-Protein Conformation,
pubmed-meshheading:10677482-Protein Structure, Secondary,
pubmed-meshheading:10677482-Sequence Alignment,
pubmed-meshheading:10677482-Signal Transduction
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pubmed:year |
2000
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pubmed:articleTitle |
A structural basis for integrin activation by the cytoplasmic tail of the alpha IIb-subunit.
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pubmed:affiliation |
Department of Molecular Cardiology, Lerner Research Institute, Cleveland, OH 44195, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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