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| | <StructureSection load='3m9d' size='340' side='right'caption='[[3m9d]], [[Resolution|resolution]] 4.50Å' scene=''> | | <StructureSection load='3m9d' size='340' side='right'caption='[[3m9d]], [[Resolution|resolution]] 4.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3m9d]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3M9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M9D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3m9d]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3M9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M9D FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3m91|3m91]], [[3m9b|3m9b]]</div></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]] 4.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mpa, MT2175 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), pup, MT2171 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3m9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m9d OCA], [https://pdbe.org/3m9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3m9d RCSB], [https://www.ebi.ac.uk/pdbsum/3m9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3m9d ProSAT]</span></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=3m9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m9d OCA], [https://pdbe.org/3m9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3m9d RCSB], [https://www.ebi.ac.uk/pdbsum/3m9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3m9d ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PUP_MYCTU PUP_MYCTU]] Protein modifier that is covalently attached to lysine residues of substrate proteins, thereby targeting them for proteasomal degradation. The tagging system is termed pupylation. Among the identified substrates are the FabD, PanB and Mpa proteins.<ref>PMID:18832610</ref> <ref>PMID:19448618</ref> <ref>PMID:20233925</ref>
| + | [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 ==
| + | |
| - | Mycobacterium tuberculosis uses a proteasome system that is analogous to the eukaryotic ubiquitin-proteasome pathway and is required for pathogenesis. However, the bacterial analog of ubiquitin, prokaryotic ubiquitin-like protein (Pup), is an intrinsically disordered protein that bears little sequence or structural resemblance to the highly structured ubiquitin. Thus, it was unknown how pupylated proteins were recruited to the proteasome. Here, we show that the Mycobacterium proteasomal ATPase (Mpa) has three pairs of tentacle-like coiled coils that recognize Pup. Mpa bound unstructured Pup through hydrophobic interactions and a network of hydrogen bonds, leading to the formation of an alpha-helix in Pup. Our work describes a binding-induced folding recognition mechanism in the Pup-proteasome system that differs mechanistically from substrate recognition in the ubiquitin-proteasome system. This key difference between the prokaryotic and eukaryotic systems could be exploited for the development of a small molecule-based treatment for tuberculosis.
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| - | | + | |
| - | Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradation.,Wang T, Darwin KH, Li H Nat Struct Mol Biol. 2010 Oct 17. PMID:20953180<ref>PMID:20953180</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 3m9d" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Li, H]] | + | [[Category: Li H]] |
| - | [[Category: Wang, T]] | + | [[Category: Wang T]] |
| - | [[Category: Beta-strand barrel]]
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| - | [[Category: Alpha helix coil coil]]
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| - | [[Category: Atp-binding]]
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| - | [[Category: Chaperone]]
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| - | [[Category: Isopeptide bond]]
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| - | [[Category: Nucleotide-binding]]
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| - | [[Category: Proteasome]]
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| - | [[Category: S-nitrosylation]]
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| - | [[Category: Ubl conjugation pathway]]
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| - | [[Category: Virulence]]
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| 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]
See Also
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
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