Mycobacterium tuberculosis protein kinase G acts as an unusual ubiquitinating enzyme to impair host immunity

ABSTRACT: Upon Mycobacterium tuberculosis (Mtb) infection, protein kinase G (PknG), a eukaryotic-type serine-threonine protein kinase (STPK), is secreted into host macrophages to promote intracellular survival of the pathogen. However, the mechanisms underlying this PknG-host interaction remain unclear. Here, we demonstrate that PknG serves both as a ubiquitin-activating enzyme (E1) and a ubiquitin ligase (E3) to trigger the ubiquitination and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TGF-?-activated kinase 1 (TAK1), thereby inhibiting the activation of NF-?B signaling and host innate responses. PknG promotes the attachment of ubiquitin (Ub) to the ubiquitin-conjugating enzyme (E2) UbcH7 via an isopeptide bond (UbcH7 K82-Ub), rather than the usual C86-Ub thiol-est

SUBMITTER: Prof. Jing Wang 

PROVIDER: S-SCDT-EMBOR-2020-52175V1 | biostudies-other |

REPOSITORIES: biostudies-other