The SH3-binding domain of chorismate mutase protein of Mycobacterium tuberculosis contributes to mycobacterial virulence
Document Type
Article
Publication Title
iScience
Abstract
Crystal structure of the secretory chorismate mutase protein of Mycobacterium tuberculosis (MtbCM) reveals presence of a proline rich region on its surface that serve as a recognition site for protein-protein interaction. This study shows that MtbCM upregulates IL-10 which favors M. tuberculosis by affecting PKCε-MKP-1-p38 MAPK signaling. MtbCM translocates to the Golgi-network where it interacts with AKAP9 via its SH3-binding domain to inhibit AKAP9-PKCε interaction and reducing PKCε phosphorylation. In the absence of phosphorylated PKCε, IRAK3 fails to stabilize MKP-1 resulting in higher p38 MAPK activation and IL-10 production. M. smegmatis expressing MtbCM survived better in infected mice. Mutation in SH3-binding domain ablated MtbCM-AKAP9 interaction resulting in IL-10 production and decreased bacterial survival. This study highlights the importance of SH3-binding domain in host-pathogen interaction and a role of MtbCM in modulation of cytokine response and mycobacterial virulence in addition to its role in shikimate pathway.
DOI
10.1016/j.isci.2024.111044
Publication Date
11-15-2024
Recommended Citation
Pal, Ravi; Maurya, Vandana; Borah, Supriya; and Mukhopadhyay, Sangita, "The SH3-binding domain of chorismate mutase protein of Mycobacterium tuberculosis contributes to mycobacterial virulence" (2024). Open Access archive. 9835.
https://impressions.manipal.edu/open-access-archive/9835
