|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
42
|
|
pubmed:dateCreated |
2009-10-21
|
|
pubmed:databankReference |
|
|
pubmed:abstractText |
Heterodimeric integrin adhesion receptors regulate diverse biological processes including angiogenesis, thrombosis and wound healing. The transmembrane-cytoplasmic domains (TMCDs) of integrins play a critical role in controlling activation of these receptors via an inside-out signaling mechanism, but the precise structural basis remains elusive. Here, we present the solution structure of integrin alphaIIb beta3 TMCD heterodimer, which reveals a right-handed coiled-coil conformation with 2 helices intertwined throughout the transmembrane region. The helices extend into the cytoplasm and form a clasp that differs significantly from a recently published alphaIIb beta3 TMCD structure. We show that while a point mutation in the clasp interface modestly activates alphaIIb beta3, additional mutations in the transmembrane interface have a synergistic effect, leading to extensive integrin activation. Detailed analyses and structural comparison with previous studies suggest that extensive integrin activation is a highly concerted conformational transition process, which involves transmembrane coiled-coil unwinding that is triggered by the membrane-mediated alteration and disengagement of the membrane-proximal clasp. Our results provide atomic insight into a type I transmembrane receptor heterocomplex and the mechanism of integrin inside-out transmembrane signaling.
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-11412103,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-11606749,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-11983888,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-12023286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-12230976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-12230977,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-12297042,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-12388784,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-14500982,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-14681217,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-15024114,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-15591321,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-15671157,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-15738420,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-15837513,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-16418530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-16434034,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-16455489,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-16716076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-16909419,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-17081964,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-17095604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-17218263,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-18174155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-18321071,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-18323455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-18417472,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-18614051,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-19034676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-19073598,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-19074766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-19111664,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-19218549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-19279667,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-19394300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-19527732,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19805198-7534799
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
1091-6490
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
20
|
|
pubmed:volume |
106
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
17729-34
|
|
pubmed:dateRevised |
2010-9-28
|
|
pubmed:meshHeading |
pubmed-meshheading:19805198-Amino Acid Sequence,
pubmed-meshheading:19805198-Animals,
pubmed-meshheading:19805198-CHO Cells,
pubmed-meshheading:19805198-Cell Membrane,
pubmed-meshheading:19805198-Cricetinae,
pubmed-meshheading:19805198-Cricetulus,
pubmed-meshheading:19805198-Cytoplasm,
pubmed-meshheading:19805198-Dimerization,
pubmed-meshheading:19805198-Humans,
pubmed-meshheading:19805198-Models, Molecular,
pubmed-meshheading:19805198-Molecular Sequence Data,
pubmed-meshheading:19805198-Multiprotein Complexes,
pubmed-meshheading:19805198-Mutagenesis, Site-Directed,
pubmed-meshheading:19805198-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:19805198-Platelet Glycoprotein GPIIb-IIIa Complex,
pubmed-meshheading:19805198-Point Mutation,
pubmed-meshheading:19805198-Protein Structure, Quaternary,
pubmed-meshheading:19805198-Protein Structure, Tertiary,
pubmed-meshheading:19805198-Recombinant Proteins,
pubmed-meshheading:19805198-Signal Transduction,
pubmed-meshheading:19805198-Transfection
|
|
pubmed:year |
2009
|
|
pubmed:articleTitle |
Structure of an integrin alphaIIb beta3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation.
|
|
pubmed:affiliation |
Department of Molecular Cardiology NB20, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
