{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:44:43Z","timestamp":1791917083033,"version":"4.3.4"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Natural Science Research Project of Jiangsu Higher Education Institutions of China","award":["24KJB520033"],"award-info":[{"award-number":["24KJB520033"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) are platelet-activating receptors whose extracellular organization contributes to receptor association and signaling during thrombus formation, yet how alternative receptor architectures influence mechanical persistence remains unclear. We used molecular dynamics to compare a GPVI dimer based on 2GI7, a domain-swapped GPVI assembly derived from 7NMU, and a crystallographic CLEC-2 contact using the same pulling protocol and constant-force conditions. During the first 5 nm of imposed separation, reconstructed GPVI required less force and mechanical work than CLEC-2 and domain-swapped GPVI. Under constant-force loading from 400 to 600 pN, reconstructed GPVI also reached the same extension endpoint markedly earlier than the domain-swapped assembly, with passage times differing by more than an order of magnitude under several conditions. Extended pulling to approximately 10 nm produced complete loss of interreceptor heavy-atom contacts in reconstructed GPVI while local peptide and disulfide connectivity remained intact. In contrast, the domain-swapped preparation retained resistance over a larger part of the separation pathway and showed substantially greater mechanical persistence. These results show that alternative extracellular arrangements of the same receptor are not mechanically equivalent and that uncertainty in GPVI architecture can translate into large differences in force transmission and persistence under load. Such architecture-dependent persistence may influence the stability of extracellular receptor associations during thrombus formation and thereby affect the mechanical lifetime of receptor clusters under load.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1014884","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:46:39Z","timestamp":1791913599000},"page":"e1014884","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct extracellular architectures shape mechanical persistence in GPVI and CLEC-2 receptor assemblies"],"prefix":"10.1371","volume":"22","author":[{"given":"Yao","family":"Zhang","sequence":"first","affiliation":[{"name":"Nantong University","place":["Nantong, China"],"department":["School of Mathematics and 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