Structural insights into substrate recognition by the type VII secretion system.
Protein Cell
; 11(2): 124-137, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31758528
ABSTRACT
Type VII secretion systems (T7SSs) are found in many disease related bacteria including Mycobacterium tuberculosis (Mtb). ESX-1 [early secreted antigen 6 kilodaltons (ESAT-6) system 1] is one of the five subtypes (ESX-1~5) of T7SSs in Mtb, where it delivers virulence factors into host macrophages during infection. However, little is known about the molecular details as to how this occurs. Here, we provide high-resolution crystal structures of the C-terminal ATPase3 domains of EccC subunits from four different Mtb T7SS subtypes. These structures adopt a classic RecA-like É/ß fold with a conserved Mg-ATP binding site. The structure of EccCb1 in complex with the C-terminal peptide of EsxB identifies the location of substrate recognition site and shows how the specific signaling module "LxxxMxF" for Mtb ESX-1 binds to this site resulting in a translation of the bulge loop. A comparison of all the ATPase3 structures shows there are significant differences in the shape and composition of the signal recognition pockets across the family, suggesting that distinct signaling sequences of substrates are required to be specifically recognized by different T7SSs. A hexameric model of the EccC-ATPase3 is proposed and shows the recognition pocket is located near the central substrate translocation channel. The diameter of the channel is ~25-Å, with a size that would allow helix-bundle shaped substrate proteins to bind and pass through. Thus, our work provides new molecular insights into substrate recognition for Mtb T7SS subtypes and also a possible transportation mechanism for substrate and/or virulence factor secretion.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Adenosina Trifosfatasas
/
Sistemas de Secreción Tipo VII
/
Mycobacterium tuberculosis
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Protein Cell
Asunto de la revista:
BIOQUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China