{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:30:57Z","timestamp":1787225457807,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,21]],"date-time":"2023-05-21T00:00:00Z","timestamp":1684627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2023,5,21]],"date-time":"2023-05-21T00:00:00Z","timestamp":1684627200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mutations in the \u03b1IIb \u03b2\u2010propeller domain have long been known to disrupt heterodimerization and intracellular trafficking of \u03b1IIb\u03b23 complexes leading to diminished surface expression and\/or function, resulting in Glanzmann thrombasthenia. Our previous study on three \u03b2\u2010propeller mutations, namely G128S, S287L, and G357S, showed variable defects in protein transport correlated with the patient's clinical phenotypes. Pulse\u2010chase experiments revealed differences in \u03b1IIb\u03b23 complex maturation among the three mutations. Hence, the current study aims to correlate conformational changes caused by each one of them. Evolutionary conservation analysis, stability analysis, and molecular dynamics simulations of the three mutant structures were carried out. Stability analysis revealed that, while G128S and G357S mutations destabilized the \u03b2\u2010propeller structure, S287L retained the stability. Wild\u2010type and mutant \u03b2\u2010propeller structures, when subjected to molecular dynamics simulations, confirmed that G128S and G357S were both destabilizing in nature when compared with the wild\u2010type and S287L based on several parameters studied, like RMSD, RMSF, Rg, FEL, PCA, secondary structure, and hydrogen bonds. In our previous study, we demonstrated that mutant S287L \u03b1IIb\u03b23 complexes were more stable than the wild\u2010type \u03b1IIb\u03b23 complexes, as evidenced in pulse\u2010chase experiments. These findings corroborate variable intracellular fates of mutant \u03b1IIb\u03b23 complexes as a result of these \u03b2\u2010propeller mutations.<\/jats:p>","DOI":"10.1002\/jcb.30423","type":"journal-article","created":{"date-parts":[[2023,5,21]],"date-time":"2023-05-21T12:55:27Z","timestamp":1684673727000},"page":"989-1001","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular dynamics simulations corroborate recombinant expression studies carried out on three \u03b1IIb \u03b2\u2010propeller mutations reported in Indian Glanzmann thrombasthenia patients"],"prefix":"10.1002","volume":"124","author":[{"given":"Finola Priyadharshini","family":"Chandrasekaran","sequence":"first","affiliation":[{"name":"Gene Therapy Laboratory, Department of Integrative Biology, School of Bio Sciences and Technology Vellore Institute of Technology Vellore 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