title: Role of the Helix in Talin F3 Domain (F3 Helix) in Talin-Mediated Integrin Activation.
abstract: Increases in ligand binding to cellular integrins (activation) play an important role in platelet and leukocyte function. Talin is necessary in vivo and sufficient in vitro for integrin αIIbβ3 activation. The precise mechanisms by which talin activates integrin are still being elucidated. In particular, talin undergoes conformational changes (around the F3 helix) and inserts the F3 helix into lipid bilayer; however, the connection between this lipid-inserting mechanism of talin and talin's capacity to activate integrin has never been explored before. In this work, we used rational mutagenesis, modeled cell systems, and structural modeling to study the potential role of membrane-induced talin conformational changes in talin-mediated integrin activation. Mutations of the residues critical for talin F3 helix to insert into membrane completely abolished talin-mediated integrin activation without affecting the binding of talin to integrins. Furthermore, mutations of the lipid-binding sequences in talin F3 helix significantly reduced the capacity of talin to activate integrin. Our results suggest that the F3 helix may contribute to talin-mediated integrin activation.
authors.affiliation: Department of Pancreatic Surgery, West China Hospital, Sichuan University, 37 Guoxue Rd, Chengdu, Sichuan Province, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Vascular Surgery, West China Hospital, Sichuan University, 37 Guoxue Rd, Chengdu, Sichuan Province, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Pancreatic Surgery, West China Hospital, Sichuan University, 37 Guoxue Rd, Chengdu, Sichuan Province, China.
authors.forename: Ailin
authors.initials: A
authors.lastname: Wei
authors.affiliation: Department of Pancreatic Surgery, West China Hospital, Sichuan University, 37 Guoxue Rd, Chengdu, Sichuan Province, China.
authors.forename: Yaliang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pancreatic Surgery, West China Hospital, Sichuan University, 37 Guoxue Rd, Chengdu, Sichuan Province, China. huweiming64@gmail.com.
authors.forename: Weiming
authors.initials: W
authors.lastname: Hu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D039661:Integrin beta3 / Q000378:metabolism*; D008958:Models, Molecular; D040201:Platelet Membrane Glycoprotein IIb / Q000737:chemistry / Q000378:metabolism*; D000072756:Protein Conformation, alpha-Helical; D054730:Protein Interaction Domains and Motifs; D016608:Talin / Q000737:chemistry* / Q000502:physiology
chemical_list: D039661:Integrin beta3; D040201:Platelet Membrane Glycoprotein IIb; D016608:Talin
keywords: F3 helix; Integrin; Integrin activation; Talin