6J17

ATPase

Summary for 6J17

• Entry DOI: 10.2210/pdb6j17/pdb
• Descriptor: ESX-3 secretion system protein EccC3, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: atpase, motor protein
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 1
• Total formula weight: 35482.58

Authors

Wang, S.H.,Li, J.,Rao, Z.H. (deposition date: 2018-12-28, release date: 2019-12-04, Last modification date: 2023-11-22)

Primary citation

Wang, S.,Zhou, K.,Yang, X.,Zhang, B.,Zhao, Y.,Xiao, Y.,Yang, X.,Yang, H.,Guddat, L.W.,Li, J.,Rao, Z.
Structural insights into substrate recognition by the type VII secretion system.
Protein Cell, 11:124-137, 2020

PubMed 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 ATPase domains of EccC subunits from four different Mtb T7SS subtypes. These structures adopt a classic RecA-like ɑ/β 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 ATPase 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-ATPase 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.

PubMed: 31758528
DOI: 10.1007/s13238-019-00671-z

Experimental method

X-RAY DIFFRACTION (1.975 Å)