5kwa

From Proteopedia

(Difference between revisions)

Current revision

complete structure of the Mycobacterium tuberculosis proteasomal ATPase Mpa

Structural highlights

5kwa is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Mycobacterium 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.

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
↑ Wu Y, Hu K, Li D, Bai L, Yang S, Jastrab JB, Xiao S, Hu Y, Zhang S, Darwin KH, Wang T, Li H. Mycobacterium tuberculosis proteasomal ATPase Mpa has a beta-grasp domain that hinders docking with the proteasome core protease. Mol Microbiol. 2017 Apr 17. doi: 10.1111/mmi.13695. PMID:28419599 doi:http://dx.doi.org/10.1111/mmi.13695

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5kwa"

Categories: Large Structures | Mycobacterium tuberculosis | WU YJ | Wang T

@@ Line 1: / Line 1: @@
 ==complete structure of the Mycobacterium tuberculosis proteasomal ATPase Mpa==
-<StructureSection load='5kwa' size='340' side='right' caption='[[5kwa]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+<StructureSection load='5kwa' size='340' side='right'caption='[[5kwa]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5kwa]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KWA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KWA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5kwa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KWA FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5kwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kwa OCA], [http://pdbe.org/5kwa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kwa RCSB], [http://www.ebi.ac.uk/pdbsum/5kwa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kwa ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5kwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kwa OCA], [https://pdbe.org/5kwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kwa RCSB], [https://www.ebi.ac.uk/pdbsum/5kwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kwa ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/ARC_MYCTU 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]<ref>PMID:14671303</ref> <ref>PMID:15659170</ref> <ref>PMID:17082771</ref> <ref>PMID:19836337</ref> <ref>PMID:20203624</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 19: @@
 </div>
 <div class="pdbe-citations 5kwa" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[ATPase 3D structures|ATPase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: WU, Y J]]
+[[Category: Large Structures]]
-[[Category: Wang, T]]
+[[Category: Mycobacterium tuberculosis]]
-[[Category: Hydrolase]]
+[[Category: WU YJ]]
-[[Category: Proteasomal atpase]]
+[[Category: Wang T]]

5kwa

From Proteopedia

Current revision

complete structure of the Mycobacterium tuberculosis proteasomal ATPase Mpa

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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