ArticlePloS one2012
Modeling and molecular dynamics of HPA-1a and -1b polymorphisms: effects on the structure of the β3 subunit of the αIIbβ3 integrin.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
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- Protein ensembles link genotype to phenotype.PLoS computational biology · 2019Review
- Structure of an extended βBlood · 2018Article
- The human platelet antigen-1b (ProThe Journal of biological chemistry · 2018Article
- The Gain-of-Function Integrin β3 Pro33 Variant Alters the Serotonin System in the Mouse Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- In silico analysis of Glanzmann variants of Calf-1 domain of αScientific reports · 2017Article
- PBxplore: a tool to analyze local protein structure and deformability with Protein Blocks.PeerJ · 2017Article
- Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome.Sao Paulo medical journal = Revista paulista de medicina · 2016Article
- αIIbβ3 variants defined by next-generation sequencing: predicting variants likely to cause Glanzmann thrombasthenia.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Protein flexibility in the light of structural alphabets.Frontiers in molecular biosciences · 2015Review
- Pro32Pro33 mutations in the integrin β3 PSI domain result in αIIbβ3 priming and enhanced adhesion: reversal of the hypercoagulability phenotype by the Src inhibitor SKI-606.Molecular pharmacology · 2014Article
- Association of platelet ITGA2B and ITGB3 polymorphisms with ex vivo antiplatelet effect of ticagrelor in healthy Chinese male subjects.International journal of hematology · 2014Article
- Article
- Detecting protein candidate fragments using a structural alphabet profile comparison approach.PloS one · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe HPA-1 alloimmune system carried by the platelet integrin αIIbβ3 is the primary cause of alloimmune thrombocytopenia in Caucasians and the HPA-1b allele might be a risk factor for thrombosis. HPA-1a and -1b alleles are defined by a leucine and a proline, respectively, at position 33 in the β3 subunit. Although the structure of αIIbβ3 is available, little is known about structural effects of the L33P substitution and its consequences on immune response and integrin functions. METHODOLOGY/PRINCIPAL
findingsA complete 3D model of the L33-β3 extracellular domain was built and a P33 model was obtained by in silico mutagenesis. We then performed molecular dynamics simulations. Analyses focused on the PSI, I-EGF-1, and I-EGF-2 domains and confirmed higher exposure of residue 33 in the L33 β3 form. These analyses also showed major structural flexibility of all three domains in both forms, but increased flexibility in the P33 β3 form. The L33P substitution does not alter the local structure (residues 33 to 35) of the PSI domain, but modifies the structural equilibrium of the three domains.
conclusionsThese results provide a better understanding of HPA-1 epitopes complexity and alloimmunization prevalence of HPA-1a. P33 gain of structure flexibility in the β3 knee may explain the increased adhesion capacity of HPA-1b platelets and the associated thrombotic risk. Our study provides important new insights into the relationship between HPA-1 variants and β3 structure that suggest possible effects on the alloimmune response and platelet function.
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