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6mna

From Proteopedia

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Crystal structure of LpqN involved in cell envelope biogenesis of Mycobacterium tuberculosis

Structural highlights

6mna is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.75Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LPQN_MYCTU Involved in cell envelope biogenesis. May act as a membrane fusion protein, connecting MmpL transporters with periplasmic proteins, and play a role in cell envelope lipid changes during biofilm maturation.^[1] Is also a virulence factor required for intracellular survival (PubMed:30118682). Associates with CBL, a host ubiquitin ligase, and probably blocks the normal functions of CBL and disturbs CBL-mediated antibacterial activity (PubMed:30118682). Interaction counteracts antibacterial defense but causes a reciprocal enhancement of antiviral defense (PubMed:30118676, PubMed:30118682).^[2] ^[3]

Publication Abstract from PubMed

The mycobacterial cell envelope is crucial to host-pathogen interactions as a barrier against antibiotics and the host immune response. In addition, cell envelope lipids are mycobacterial virulence factors. Cell envelope lipid biosynthesis is the target of a number of frontline tuberculosis treatments and has been the focus of much research. However, the transport mechanisms by which these lipids reach the mycomembrane remain poorly understood. Many envelope lipids are exported from the cytoplasm to the periplasmic space via the mycobacterial membrane protein large (MmpL) family of proteins. In other bacteria, lipoproteins can contribute to outer membrane biogenesis through direct binding of substrates and/or protein-protein associations with extracytoplasmic biosynthetic enzymes. In this report, we investigate whether the lipoprotein LpqN plays a similar role in mycobacteria. Using a genetic two-hybrid approach, we demonstrate that LpqN interacts with periplasmic loop domains of the MmpL3 and MmpL11 transporters that export mycolic acid-containing cell envelope lipids. We observe that LpqN also interacts with secreted cell envelope biosynthetic enzymes such as Ag85A via pulldown assays. The X-ray crystal structures of LpqN and LpqN bound to dodecyl-trehalose suggest that LpqN directly binds trehalose monomycolate, the MmpL3 and Ag85A substrate. Finally, we observe altered lipid profiles of the DeltalpqN mutant during biofilm maturation, pointing toward a possible physiological role for the protein. The results of this study suggest that LpqN may act as a membrane fusion protein, connecting MmpL transporters with periplasmic proteins, and provide general insight into the role of lipoproteins in Mycobacterium tuberculosis cell envelope biogenesis.

Structural and functional evidence that lipoprotein LpqN supports cell envelope biogenesis in Mycobacterium tuberculosis.,Melly GC, Stokas H, Dunaj JL, Hsu FF, Rajavel M, Su CC, Yu EW, Purdy GE J Biol Chem. 2019 Oct 25;294(43):15711-15723. doi: 10.1074/jbc.RA119.008781. Epub, 2019 Aug 30. PMID:31471317^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Melly GC, Stokas H, Dunaj JL, Hsu FF, Rajavel M, Su CC, Yu EW, Purdy GE. Structural and functional evidence that lipoprotein LpqN supports cell envelope biogenesis in Mycobacterium tuberculosis. J Biol Chem. 2019 Oct 25;294(43):15711-15723. doi: 10.1074/jbc.RA119.008781. Epub, 2019 Aug 30. PMID:31471317 doi:http://dx.doi.org/10.1074/jbc.RA119.008781
↑ Penn BH, Netter Z, Johnson JR, Von Dollen J, Jang GM, Johnson T, Ohol YM, Maher C, Bell SL, Geiger K, Golovkine G, Du X, Choi A, Parry T, Mohapatra BC, Storck MD, Band H, Chen C, Jäger S, Shales M, Portnoy DA, Hernandez R, Coscoy L, Cox JS, Krogan NJ. An Mtb-Human Protein-Protein Interaction Map Identifies a Switch between Host Antiviral and Antibacterial Responses. Mol Cell. 2018 Aug 16;71(4):637-648.e5. PMID:30118682 doi:10.1016/j.molcel.2018.07.010
↑ Eoh H, Jung JU. Bacterial Protein Reshapes Host Defense toward Antiviral Responses. Mol Cell. 2018 Aug 16;71(4):483-484. PMID:30118676 doi:10.1016/j.molcel.2018.08.006
↑ Melly GC, Stokas H, Dunaj JL, Hsu FF, Rajavel M, Su CC, Yu EW, Purdy GE. Structural and functional evidence that lipoprotein LpqN supports cell envelope biogenesis in Mycobacterium tuberculosis. J Biol Chem. 2019 Oct 25;294(43):15711-15723. doi: 10.1074/jbc.RA119.008781. Epub, 2019 Aug 30. PMID:31471317 doi:http://dx.doi.org/10.1074/jbc.RA119.008781

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6mna"

Categories: Large Structures | Mycobacterium tuberculosis H37Rv | Rajavel M | Su CC | Yu EW

@@ Line 3: / Line 3: @@
 <StructureSection load='6mna' size='340' side='right'caption='[[6mna]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6mna]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MNA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MNA FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6mna]] is a 1 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=6MNA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MNA FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=T6D:alpha-D-glucopyranosyl+6-O-decanoyl-alpha-D-glucopyranoside'>T6D</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]] 1.75&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lpqN, Rv0583c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900093:6-decanoyl-trehalose'>PRD_900093</scene>, <scene name='pdbligand=U2D:6-O-decanoyl-alpha-D-glucopyranose'>U2D</scene></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=6mna FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mna OCA], [http://pdbe.org/6mna PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mna RCSB], [http://www.ebi.ac.uk/pdbsum/6mna PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mna 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=6mna FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mna OCA], [https://pdbe.org/6mna PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mna RCSB], [https://www.ebi.ac.uk/pdbsum/6mna PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mna ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/LPQN_MYCTU LPQN_MYCTU] Involved in cell envelope biogenesis. May act as a membrane fusion protein, connecting MmpL transporters with periplasmic proteins, and play a role in cell envelope lipid changes during biofilm maturation.<ref>PMID:31471317</ref>   Is also a virulence factor required for intracellular survival (PubMed:30118682). Associates with CBL, a host ubiquitin ligase, and probably blocks the normal functions of CBL and disturbs CBL-mediated antibacterial activity (PubMed:30118682). Interaction counteracts antibacterial defense but causes a reciprocal enhancement of antiviral defense (PubMed:30118676, PubMed:30118682).<ref>PMID:30118682</ref> <ref>PMID:30118676</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Myctu]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Rajavel, M]]
+[[Category: Rajavel M]]
-[[Category: Su, C C]]
+[[Category: Su CC]]
-[[Category: Yu, E W]]
+[[Category: Yu EW]]
-[[Category: Lipid binding protein]]
-[[Category: Trehalose 6-dodecanoate]]

6mna

From Proteopedia

Current revision

Crystal structure of LpqN involved in cell envelope biogenesis of Mycobacterium tuberculosis

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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