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| | <StructureSection load='5jk2' size='340' side='right'caption='[[5jk2]], [[Resolution|resolution]] 2.15Å' scene=''> | | <StructureSection load='5jk2' size='340' side='right'caption='[[5jk2]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jk2]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Trepa Trepa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JK2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JK2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jk2]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Treponema_pallidum_subsp._pallidum_str._Nichols Treponema pallidum subsp. pallidum str. Nichols]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JK2 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jir|5jir]]</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]] 2.15Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TP_0751 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243276 TREPA])</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=5jk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jk2 OCA], [https://pdbe.org/5jk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jk2 RCSB], [https://www.ebi.ac.uk/pdbsum/5jk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jk2 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=5jk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jk2 OCA], [http://pdbe.org/5jk2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jk2 RCSB], [http://www.ebi.ac.uk/pdbsum/5jk2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jk2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Y751_TREPA Y751_TREPA] |
| - | Syphilis is a chronic disease caused by the bacterium Treponema pallidum subsp. pallidum. Treponema pallidum disseminates widely throughout the host and extravasates from the vasculature, a process that is at least partially dependent upon the ability of T. pallidum to interact with host extracellular matrix (ECM) components. Defining the molecular basis for the interaction between T. pallidum and the host is complicated by the intractability of T. pallidum to in vitro culturing and genetic manipulation. Correspondingly, few T. pallidum proteins have been identified that interact directly with host components. Of these, Tp0751 (also known as pallilysin) displays a propensity to interact with the ECM, although the underlying mechanism of these interactions remains unknown. Towards establishing the molecular mechanism of Tp0751-host ECM attachment, we first determined the crystal structure of Tp0751 to a resolution of 2.15 A using selenomethionine phasing. Structural analysis revealed an eight-stranded beta-barrel with a profile of short conserved regions consistent with a non-canonical lipocalin fold. Using a library of native and scrambled peptides representing the full Tp0751 sequence, we next identified a subset of peptides that showed statistically significant and dose-dependent interactions with the ECM components fibrinogen, fibronectin, collagen I, and collagen IV. Intriguingly, each ECM-interacting peptide mapped to the lipocalin domain. To assess the potential of these ECM-coordinating peptides to inhibit adhesion of bacteria to host cells, we engineered an adherence-deficient strain of the spirochete Borrelia burgdorferi to heterologously express Tp0751. This engineered strain displayed Tp0751 on its surface and exhibited a Tp0751-dependent gain-of-function in adhering to human umbilical vein endothelial cells that was inhibited in the presence of one of the ECM-interacting peptides (p10). Overall, these data provide the first structural insight into the mechanisms of Tp0751-host interactions, which are dependent on the protein's lipocalin fold.
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| - | The Structure of Treponema pallidum Tp0751 (Pallilysin) Reveals a Non-canonical Lipocalin Fold That Mediates Adhesion to Extracellular Matrix Components and Interactions with Host Cells.,Parker ML, Houston S, Petrosova H, Lithgow KV, Hof R, Wetherell C, Kao WC, Lin YP, Moriarty TJ, Ebady R, Cameron CE, Boulanger MJ PLoS Pathog. 2016 Sep 28;12(9):e1005919. doi: 10.1371/journal.ppat.1005919., eCollection 2016 Sep. PMID:27683203<ref>PMID:27683203</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5jk2" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Trepa]] | + | [[Category: Treponema pallidum subsp. pallidum str. Nichols]] |
| - | [[Category: Boulanger, M J]] | + | [[Category: Boulanger MJ]] |
| - | [[Category: Parker, M L]] | + | [[Category: Parker ML]] |
| - | [[Category: Adhesin]]
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| - | [[Category: Cell adhesion]]
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| - | [[Category: Lipocalin]]
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| - | [[Category: Outer membrane protein]]
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