On the role of the sorting platform in hierarchical type III secretion regulation in enteropathogenic Escherichia coli
Por:
Marcos-Vilchis A., Espinosa N., Alvarez A.F., Puente J.L., Soto J.E., González-Pedrajo B.
Publicada:
1 ene 2025
Ahead of Print:
1 mar 2025
Resumen:
The virulence of enteropathogenic Escherichia coli (EPEC) depends on a type III secretion system (T3SS), a membrane-spanning apparatus that injects effector proteins into the cytoplasm of target enterocytes. The T3SS, or injectisome, is a self-assembled nanomachine whose biogenesis and function rely on the ordered secretion of three distinct categories of proteins: early, middle, and late type III substrates. In EPEC, this hierarchical secretion is assisted by several cytosolic protein complexes at the base of the injectisome. Among these, the sorting platform is involved in the recognition and sequential loading of the different classes of T3-substrates. In addition, a heterotrimeric gatekeeper complex, also known as a molecular switch, operates in concert with components of the T3SS export apparatus to guarantee the delivery of middle substrates prior to late substrate secretion. In this study, we showed that the sorting platform is differentially required for the secretion of distinct categories of substrates. Moreover, we demonstrated a cooperative interplay and protein–protein interactions between the sorting platform and the gatekeeper complex for proper middle and late substrate docking and secretion. Overall, our results provide new insights into the intricate molecular mechanisms that regulate protein secretion hierarchy during T3SS assembly. Copyright © 2025 Marcos-Vilchis et al.
Filiaciones:
Marcos-Vilchis A.:
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
Espinosa N.:
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
Alvarez A.F.:
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
Puente J.L.:
Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Morelos, Mexico
Soto J.E.:
Programa de Ingeniería Genómica, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Morelos, Mexico
González-Pedrajo B.:
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
hybrid, All Open Access; Hybrid Gold Open Access
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