RT Journal Article
T1 Mechanical forces and ligand binding modulate Pseudomonas aeruginosa PilY1 mechanosensitive protein
A1 Cao García, Francisco Javier
A1 Walker, Jane E.
A1 Board, Stephanie
A1 Alonso-Caballero, Álvaro
AB Surface sensing initiates bacterial colonization of substrates. The protein PilY1 plays key roles during this process—surface detection, host adhesion, and motility—while experiencing mechanical perturbations of varying magnitudes. In Pseudomonas aeruginosa, the adhesion and motility functions of PilY1 are associated with integrin and calcium ligand-binding sites; however, how mechanical forces influence PilY1’s dynamics and its interactions with these ligands remain unknown. Here, using single-molecule magnetic tweezers, we reveal that PilY1 is a mechanosensor protein that exhibits different behaviors depending on the force load. At high forces (>20 pN), PilY1 unfolds through a hierarchical sequence of intermediates, whose mechanical stability increases with calcium binding. This enhanced stability may help counteract type IV pilus retraction forces during motility. At low forces (<7 pN), we identify the dynamics of the integrin-binding domain, which is reminiscent of the behavior of mechanosensor proteins. Integrin binding induces a force-dependent conformational change in this domain, shortening its unfolded extension. Our findings suggest that PilY1 roles are force- and ligand-modulated, which could entail a mechanical-based compartmentalization of its functions.
PB Cold Spring Harbor Laboratory Press
YR 2025
FD 2025-03-07
LK https://hdl.handle.net/20.500.14352/119054
UL https://hdl.handle.net/20.500.14352/119054
LA eng
NO Cao-Garcia FJ, Walker JE, Board S, Alonso-Caballero A (2025) Mechanical forces and ligand binding modulate Pseudomonas aeruginosa PilY1 mechanosensitive protein. Life Sci Alliance 8: e202403111. doi:10.26508/lsa.202403111.
NO European Commission
NO Francis Crick Institute (Reino Unido)
NO Ministerio de Economía y Competitividad (España)
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Universidad Complutense de Madrid
NO Leverhulme Trust (Reino Unido)
NO Cancer Research UK
NO UK Medical Research Council
NO Wellcome Trust (Reino Unido)
NO Agencia Estatal de Investigación (España)
DS Docta Complutense
RD 18 dic 2025