|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Mycobacterium tuberculosis Eis protein initiates modulation of host immune responses by acetylation of DUSP16/MKP-7== | | ==Mycobacterium tuberculosis Eis protein initiates modulation of host immune responses by acetylation of DUSP16/MKP-7== |
| - | <StructureSection load='3sxn' size='340' side='right' caption='[[3sxn]], [[Resolution|resolution]] 2.03Å' scene=''> | + | <StructureSection load='3sxn' size='340' side='right'caption='[[3sxn]], [[Resolution|resolution]] 2.03Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3sxn]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SXN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SXN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3sxn]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SXN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SXN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COA:COENZYME+A'>COA</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]] 2.03Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ryo|3ryo]], [[3uy5|3uy5]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Eis, MSMEG_3513 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</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=3sxn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sxn OCA], [https://pdbe.org/3sxn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sxn RCSB], [https://www.ebi.ac.uk/pdbsum/3sxn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sxn ProSAT]</span></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=3sxn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sxn OCA], [http://pdbe.org/3sxn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sxn RCSB], [http://www.ebi.ac.uk/pdbsum/3sxn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sxn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/A0QY29_MYCS2 A0QY29_MYCS2] |
| - | The intracellular pathogen Mycobacterium tuberculosis (Mtb) causes tuberculosis. Enhanced intracellular survival (Eis) protein, secreted by Mtb, enhances survival of Mycobacterium smegmatis (Msm) in macrophages. Mtb Eis was shown to suppress host immune defenses by negatively modulating autophagy, inflammation, and cell death through JNK-dependent inhibition of reactive oxygen species (ROS) generation. Mtb Eis was recently demonstrated to contribute to drug resistance by acetylating multiple amines of aminoglycosides. However, the mechanism of enhanced intracellular survival by Mtb Eis remains unanswered. Therefore, we have characterized both Mtb and Msm Eis proteins biochemically and structurally. We have discovered that Mtb Eis is an efficient N(epsilon)-acetyltransferase, rapidly acetylating Lys55 of dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7), a JNK-specific phosphatase. In contrast, Msm Eis is more efficient as an N(alpha)-acetyltransferase. We also show that Msm Eis acetylates aminoglycosides as readily as Mtb Eis. Furthermore, Mtb Eis, but not Msm Eis, inhibits LPS-induced JNK phosphorylation. This functional difference against DUSP16/MKP-7 can be understood by comparing the structures of two Eis proteins. The active site of Mtb Eis with a narrow channel seems more suitable for sequence-specific recognition of the protein substrate than the pocket-shaped active site of Msm Eis. We propose that Mtb Eis initiates the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation by acetylating DUSP16/MKP-7. Our work thus provides insight into the mechanism of suppressing host immune responses and enhancing mycobacterial survival within macrophages by Mtb Eis.
| + | |
| - | | + | |
| - | Mycobacterium tuberculosis Eis protein initiates suppression of host immune responses by acetylation of DUSP16/MKP-7.,Kim KH, An DR, Song J, Yoon JY, Kim HS, Yoon HJ, Im HN, Kim J, Kim do J, Lee SJ, Kim KH, Lee HM, Kim HJ, Jo EK, Lee JY, Suh SW Proc Natl Acad Sci U S A. 2012 May 15;109(20):7729-34. Epub 2012 Apr 30. PMID:22547814<ref>PMID:22547814</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3sxn" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Mycs2]] | + | [[Category: Large Structures]] |
| - | [[Category: An, D R]] | + | [[Category: Mycolicibacterium smegmatis MC2 155]] |
| - | [[Category: Im, H N]] | + | [[Category: An DR]] |
| - | [[Category: Kim, D J]] | + | [[Category: Im HN]] |
| - | [[Category: Kim, H J]] | + | [[Category: Kim DJ]] |
| - | [[Category: Kim, H S]] | + | [[Category: Kim HJ]] |
| - | [[Category: Kim, J]] | + | [[Category: Kim HS]] |
| - | [[Category: Kim, K H]] | + | [[Category: Kim J]] |
| - | [[Category: Lee, J Y]] | + | [[Category: Kim KH]] |
| - | [[Category: Lee, S J]] | + | [[Category: Lee JY]] |
| - | [[Category: Song, J S]] | + | [[Category: Lee SJ]] |
| - | [[Category: Suh, S W]] | + | [[Category: Song JS]] |
| - | [[Category: Yoon, H J]] | + | [[Category: Suh SW]] |
| - | [[Category: Yoon, J Y]] | + | [[Category: Yoon HJ]] |
| - | [[Category: Acetyl coa binding]]
| + | [[Category: Yoon JY]] |
| - | [[Category: Acetyltransferase]]
| + | |
| - | [[Category: Gnat fold]]
| + | |
| - | [[Category: Transferase]]
| + | |
