Molecular basis of unidirectional information transmission in two-component systems: lessons from the DesK-DesR thermosensor

 

Autor(es):
Lima, Sofía ; Blanco, Juan ; Olivieri, Federico ; Imelio, Juan Andrés ; Carrión, Federico ; Alvarez, Beatriz ; Buschiazzo, Alejandro ; Martí, Marcelo ; Trajtenberg, Felipe
Tipo:
Preprint
Financiadores:
Agencia Nacional de Investigación e Innovación
Resumen:

Cellular signaling systems transmit information over long distances using allosteric transitions and/or post-translational modifications. In two-component systems the sensor histidine kinase and response regulator are wired through phosphoryl-transfer reactions, using either a uni- or bi-directional transmission mode, allowing to build rich regulatory networks. Using the thermosensor DesK-DesR two-component system from Bacillus subtilis and combining crystal structures, QM/MM calculations and integrative kinetic modeling, we uncover that: i) longer or shorter distances between the phosphoryl-acceptor and -donor residues can shift the phosphoryl-transfer equilibrium; ii) the phosphorylation-dependent dimerization of the regulator acts as a sequestering mechanism by preventing the interaction with the histidine kinase; and iii) the kinase’s intrinsic conformational equilibrium makes the phosphotransferase state unlikely in the absence of histidine phosphorylation, minimizing backwards transmission. These mechanisms allow the system to control the direction of signal transmission in a very efficient way, showcasing the key role that structure-encoded allostery plays in signaling proteins to store and transmit information.

Año:
2021
Idioma:
Inglés
Temas:
Fosforilación de proteínas
Biología de sistemas
Cinética enzimática
Regulación alostérica
Equilibrio conformacional
Ciencias Naturales y Exactas
Ciencias Biológicas
Bioquímica y Biología Molecular
Biología Celular, Microbiología
Institución:
Institut Pasteur de Montevideo
Repositorio:
REDI-IPMON
Enlace(s):
https://hdl.handle.net/20.500.12381/604
Nivel de acceso:
Acceso abierto