| Structural highlights
Function
ARC_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 PubMed
Proteasomes are present in eukaryotes, archaea and Actinobacteria, including the human pathogen Mycobacterium tuberculosis, where proteasomal degradation supports persistence inside the host. In mycobacteria and other members of Actinobacteria, prokaryotic ubiquitin-like protein (Pup) serves as a degradation tag post-translationally conjugated to target proteins for their recruitment to the mycobacterial proteasome ATPase (Mpa). Here, we use single-particle cryo-electron microscopy to determine the structure of Mpa in complex with the 20S core particle at an early stage of pupylated substrate recruitment, shedding light on the mechanism of substrate translocation. Two conformational states of Mpa show how substrate is translocated stepwise towards the degradation chamber of the proteasome core particle. We also demonstrate, in vitro and in vivo, the importance of a structural feature in Mpa that allows formation of alternating charge-complementary interactions with the proteasome resulting in radial, rail-guided movements during the ATPase conformational cycle.
Structural basis of prokaryotic ubiquitin-like protein engagement and translocation by the mycobacterial Mpa-proteasome complex.,Kavalchuk M, Jomaa A, Muller AU, Weber-Ban E Nat Commun. 2022 Jan 12;13(1):276. doi: 10.1038/s41467-021-27787-3. PMID:35022401[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Darwin KH, Ehrt S, Gutierrez-Ramos JC, Weich N, Nathan CF. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science. 2003 Dec 12;302(5652):1963-6. PMID:14671303 doi:10.1126/science.1091176
- ↑ Darwin KH, Lin G, Chen Z, Li H, Nathan CF. Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue. Mol Microbiol. 2005 Jan;55(2):561-71. PMID:15659170 doi:10.1111/j.1365-2958.2004.04403.x
- ↑ Pearce MJ, Arora P, Festa RA, Butler-Wu SM, Gokhale RS, Darwin KH. Identification of substrates of the Mycobacterium tuberculosis proteasome. EMBO J. 2006 Nov 15;25(22):5423-32. PMID:17082771 doi:10.1038/sj.emboj.7601405
- ↑ Wang T, Li H, Lin G, Tang C, Li D, Nathan C, Darwin KH, Li H. Structural insights on the Mycobacterium tuberculosis proteasomal ATPase Mpa. Structure. 2009 Oct 14;17(10):1377-85. PMID:19836337 doi:10.1016/j.str.2009.08.010
- ↑ Striebel F, Hunkeler M, Summer H, Weber-Ban E. The mycobacterial Mpa-proteasome unfolds and degrades pupylated substrates by engaging Pup's N-terminus. EMBO J. 2010 Apr 7;29(7):1262-71. PMID:20203624 doi:10.1038/emboj.2010.23
- ↑ Kavalchuk M, Jomaa A, Müller AU, Weber-Ban E. Structural basis of prokaryotic ubiquitin-like protein engagement and translocation by the mycobacterial Mpa-proteasome complex. Nat Commun. 2022 Jan 12;13(1):276. PMID:35022401 doi:10.1038/s41467-021-27787-3
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