Azcutia Criado, VerónicaRosetti, FlorenciaChen, YunfengSen, MehmetThayer, ElizabethHerter, Jan M.Luscinskas, Francis W.Cullere, XavierZhu, ChengMayadas, Tanya N.2025-01-292025-01-292015Rosetti, Florencia, et al. «A Lupus-Associated Mac-1 Variant Has Defects in Integrin Allostery and Interaction with Ligands under Force». Cell Reports, vol. 10, n.o 10, marzo de 2015, pp. 1655-64. DOI.org (Crossref), https://doi.org/10.1016/j.celrep.2015.02.037.10.1016/j.celrep.2015.02.037https://hdl.handle.net/20.500.14352/116767Leukocyte CD18 integrins increase their affinity for ligand by transmitting allosteric signals to and from their ligand-binding αI domain. Mechanical forces induce allosteric changes that paradoxically slow dissociation by increasing the integrin/ligand bond lifetimes, referred to as catch bonds. Mac-1 formed catch bonds with its ligands. However, a Mac-1 gene (ITGAM) coding variant (rs1143679, R77H), which is located in the β-propeller domain and is significantly associated with systemic lupus erythematosus risk, exhibits a marked impairment in 2D ligand affinity and affinity maturation under mechanical force. Targeted mutations and activating antibodies reveal that the failure in Mac-1 R77H allostery is rescued by induction of cytoplasmic tail separation and full integrin extension. These findings demonstrate roles for R77, and the β-propeller in which it resides, in force-induced allostery relay and integrin bond stabilization. Defects in these processes may have pathological consequences, as the Mac-1 R77H variant is associated with increased susceptibility to lupus.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://doi.org/10.1016/j.celrep.2015.02.037open access612.015577.1612.017Integrina Mac-1Alostería de integrinasFuerzas mecánicas en la adhesión celularSistema inmunológicoLupusInmunologíaBioquímica (Farmacia)Fisiología animal (Farmacia)2412 Inmunología