ArticleBlood2007
Mapping early conformational changes in alphaIIb and beta3 during biogenesis reveals a potential mechanism for alphaIIbbeta3 adopting its bent conformation.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Biomechanical activation of blood platelets via adhesion to von Willebrand factor studied with mesoscopic simulations.Biomechanics and modeling in mechanobiology · 2023Article
- Patients with triple-negative, JAK2V617F- and CALR-mutated essential thrombocythemia share a unique gene expression signature.Blood advances · 2021Article
- Biomechanical thrombosis: the dark side of force and dawn of mechano-medicine.Stroke and vascular neurology · 2020Review
- Deciphering the Roles of N-Glycans on Collagen-Platelet Interactions.Journal of proteome research · 2019Article
- Autonomous conformational regulation of βProceedings of the National Academy of Sciences of the United States of America · 2018Article
- In silico analysis of structural modifications in and around the integrin αIIb genu caused by ITGA2B variants in human platelets with emphasis on Glanzmann thrombasthenia.Molecular genetics & genomic medicine · 2018Article
- In silico analysis of Glanzmann variants of Calf-1 domain of αScientific reports · 2017Article
- Force regulated conformational change of integrin αMatrix biology : journal of the International Society for Matrix Biology · 2017Article
- Inhibition of αIIbβ3 Ligand Binding by an αIIb Peptide that Clasps the Hybrid Domain to the βI Domain of β3.PloS one · 2015Article
- Glanzmann thrombasthenia: state of the art and future directions.Seminars in thrombosis and hemostasis · 2013Review
- Carrier subunit of plasma membrane transporter is required for oxidative folding of its helper subunit.The Journal of biological chemistry · 2012Article
- Intact alphaIIbbeta3 integrin is extended after activation as measured by solution X-ray scattering and electron microscopy.The Journal of biological chemistry · 2011Article
- Effects of limiting extension at the alphaIIb genu on ligand binding to integrin alphaIIbbeta3.The Journal of biological chemistry · 2010Article
- Targeted molecular dynamics reveals overall common conformational changes upon hybrid domain swing-out in beta3 integrins.Proteins · 2009Article
- Multiple approaches converge on the structure of the integrin alphaIIb/beta3 transmembrane heterodimer.Journal of molecular biology · 2009Article
- Review
- Integrin conformational regulation: uncoupling extension/tail separation from changes in the head region by a multiresolution approach.Structure (London, England : 1993) · 2008Article
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Authors and funding
6 authors.
Funding
Abstract
Current evidence supports a model in which the low-affinity state of the platelet integrin alphaIIbbeta3 results from alphaIIbbeta3 adopting a bent conformation. To assess alphaIIbbeta3 biogenesis and how alphaIIbbeta3 initially adopts the bent conformation, we mapped the conformational states occupied by alphaIIb and beta3 during biogenesis using conformation-specific monoclonal antibodies (mAbs). We found that alphaIIbbeta3 complex formation was not limited by the availability of either free pro-alphaIIb or free beta3, suggesting that other molecules, perhaps chaperones, control complex formation. Five beta3-specific, ligand-induced binding site (LIBS) mAbs reacted with much or all free beta3 but not with beta3 when in complex with mature alphaIIb, suggesting that beta3 adopts its mature conformation only after complex formation. Conversely, 2 alphaIIb-specific LIBS mAbs directed against the alphaIIb Calf-2 region adjacent to the membrane reacted with only minor fractions of free pro-alphaIIb, raising the possibility that pro-alphaIIb adopts a bent conformation early in biogenesis. Our data suggest a working model in which pro-alphaIIb adopts a bent conformation soon after synthesis, and then beta3 assumes its bent conformation by virtue of its interaction with the bent pro-alphaIIb.
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