Structural insights into the assembly pathway of the Helicobacter pylori CagT4SS outer membrane core complex.
Structure
; 32(10): 1725-1736.e4, 2024 Oct 03.
Article
in En
| MEDLINE
| ID: mdl-39032488
ABSTRACT
Cag type IV secretion system (CagT4SS) translocates oncoprotein cytotoxin-associated gene A (CagA) into host cells and plays a key role in the pathogenesis of Helicobacter pylori. The structure of the outer membrane core complex (OMCC) in CagT4SS consists of CagX, CagY, CagM, CagT, and Cag3 in a stoichiometric ratio of 11225 with 14-fold symmetry. However, the assembly pathway of OMCC remains elusive. Here, we report the crystal structures of CagT and Cag3-CagT complex, and the structural dynamics of Cag3 and CagT using hydrogen deuterium exchange-mass spectrometry (HDX-MS). The interwoven interaction of Cag3 and CagT involves conformational changes of CagT and ß strand swapping. In conjunction with biochemical and biophysical assays, we further demonstrate the different oligomerization states of Cag3 and Cag3-CagT complex. Additionally, the association with CagM requires the pre-formation of Cag3-CagT complex. These results demonstrate the generation of different intermediate sub-assemblies and their structural flexibility, potentially representing different building blocks for OMCC assembly.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Models, Molecular
/
Helicobacter pylori
Language:
En
Journal:
Structure
Year:
2024
Document type:
Article