{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:56:28Z","timestamp":1790016988149,"version":"4.0.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Vellore Institute of Technology, Vellore"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Integrin \u03b1IIb\u03b23 is the predominant receptor for fibrinogen which mediates platelet aggregation, an important step in hemostasis and thrombosis. Several mutations have been reported in the genes encoding \u03b1IIb and \u03b23 subunits among patients with Glanzmann thrombasthenia, of which 177 are in the \u03b2-propeller domain. The two subunits form a heterodimer at the interface between \u03b2-propeller and \u03b2-I domains of \u03b1IIb and \u03b23, respectively with their stability critical for intracellular trafficking, surface expression, and ligand binding. Our study was aimed at retrieving the \u03b2-propeller mutations from various databases and studying structural variations due to select mutations upon interaction with fibrinogen using molecular docking and molecular dynamics. Mutations were studied for their impact on phenotypic severity, structural stability, and evolutionary conservation. Molecular docking analysis and molecular dynamics simulations were carried out for \u03b1IIb-\u03b23 complexes as well as \u03b1IIb\u03b23-fibrinogen complexes; in particular, E355K structure had more deviations, fluctuations, and other changes which compromised its structural stability and binding affinity when compared to both wild-type and G401C structures. Our comprehensive in silico analysis clearly reiterates that mutations in the \u03b2-propeller are not only responsible for structural changes in this domain but also have implications on the overall structure and function of integrin \u03b1IIb\u03b23.<\/jats:p>","DOI":"10.1038\/s41598-024-75070-4","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T06:02:28Z","timestamp":1728972148000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular dynamics simulations involving different \u03b2-propeller mutations reported in Swiss and French patients correlate with their disease phenotypes"],"prefix":"10.1038","volume":"14","author":[{"given":"Finola Priyadharshini","family":"Chandrasekaran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everette Jacob Remington","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"75070_CR1","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/j.molcel.2008.11.018","volume":"32","author":"J Zhu","year":"2008","unstructured":"Zhu, J. et al. Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by Applied forces. Mol. Cell. 32, 849\u2013861 (2008).","journal-title":"Mol. Cell."},{"key":"75070_CR2","first-page":"151","volume":"296","author":"JP Xiong","year":"2002","unstructured":"Xiong, J. P. et al. Crystal structure of the extracellular segment of integrin \u03b1V\u03b23 in complex with an arg-gly-asp ligand. Sci. (1979). 296, 151\u2013155 (2002).","journal-title":"Sci. (1979)"},{"key":"75070_CR3","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1182\/blood-2012-02-409995","volume":"120","author":"K Kiyomizu","year":"2012","unstructured":"Kiyomizu, K. et al. Recognition of highly restricted regions in the \u03b2-propeller domain of \u03b1IIb by platelet-associated anti-\u03b1IIb\u03b23 autoantibodies in primary immune thrombocytopenia. 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The correct email for Everette Jacob Remington Nelson is everette.nelson@gmail.com.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"24133"}}