5kwa
complete structure of the Mycobacterium tuberculosis proteasomal ATPase Mpa
Structural highlights
FunctionARC_MYCTU ATPase which is responsible for recognizing, binding, unfolding and translocation of pupylated proteins into the bacterial 20S proteasome core particle. May be essential for opening the gate of the 20S proteasome via an interaction with its C-terminus, thereby allowing substrate entry and access to the site of proteolysis. Thus, the C-termini of the proteasomal ATPase may function like a 'key in a lock' to induce gate opening and therefore regulate proteolysis. Is required but not sufficient to confer resistance against the lethal effects of reactive nitrogen intermediates (RNI), antimicrobial molecules produced by activated macrophages and other cell types.[HAMAP-Rule:MF_02112][1] [2] [3] [4] [5] Publication Abstract from PubMedMycobacterium tuberculosis (Mtb) has a proteasome system that is essential for its ability to cause lethal infections in mice. A key component of the system is the proteasomal adenosine triphosphatase (ATPase) Mpa, which captures, unfolds, and translocates protein substrates into the Mtb proteasome core particle for degradation. Here, we report the crystal structures of near full-length hexameric Mtb Mpa in apo and ADP-bound forms. Surprisingly, the structures revealed a ubiquitin-like beta-grasp domain that precedes the proteasome-activating carboxyl terminus. This domain, which was only found in bacterial proteasomal ATPases, buries the carboxyl terminus of each protomer in the central channel of the hexamer and hinders the interaction of Mpa with the proteasome core protease. Thus, our work reveals the structure of a bacterial proteasomal ATPase in the hexameric form, and the structure finally explains why Mpa is unable to stimulate robust protein degradation in vitro in the absence of other, yet-to-be-identified co-factors. Mycobacterium tuberculosis proteasomal ATPase Mpa has a beta-grasp domain that hinders docking with the proteasome core protease.,Wu Y, Hu K, Li D, Bai L, Yang S, Jastrab JB, Xiao S, Hu Y, Zhang S, Darwin KH, Wang T, Li H Mol Microbiol. 2017 Apr 17. doi: 10.1111/mmi.13695. PMID:28419599[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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