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| | ==Crystal structure of the KRT10-binding region domain of the pneumococcal serine rich repeat protein PsrP== | | ==Crystal structure of the KRT10-binding region domain of the pneumococcal serine rich repeat protein PsrP== |
| - | <StructureSection load='3zgh' size='340' side='right' caption='[[3zgh]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3zgh' size='340' side='right'caption='[[3zgh]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zgh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Strpn Strpn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZGH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZGH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zgh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_TIGR4 Streptococcus pneumoniae TIGR4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZGH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZGH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zgi|3zgi]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=3zgh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zgh OCA], [http://pdbe.org/3zgh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zgh RCSB], [http://www.ebi.ac.uk/pdbsum/3zgh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zgh 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=3zgh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zgh OCA], [https://pdbe.org/3zgh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zgh RCSB], [https://www.ebi.ac.uk/pdbsum/3zgh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zgh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/PSRP_STRPN PSRP_STRPN] Protein that allows bacteria to adhere to mammalian host cells. Required for full virulence in mouse infection models when infected intranasally (PubMed:16861665). Required for adhesion to host cells in vitro and for persistence in the lower respiratory tract (PubMed:18507531). Binds host keratin 10 (KRT10) on lung cells which mediates adhesion via the C-terminus of the basic region (BR, residues 273-341); glycosylation of either protein is not required for the interaction (PubMed:19627498). A region in the N-terminus (residues 122-166) self aggregates, contributing to mature biofilm formation (PubMed:20714350). The basic region (BR, residues 187-385) also self aggregates; the BR binds DNA which enhances self aggregation (PubMed:27582320).<ref>PMID:16861665</ref> <ref>PMID:18507531</ref> <ref>PMID:19627498</ref> <ref>PMID:20714350</ref> <ref>PMID:27582320</ref> |
| - | Streptococcus pneumoniae is a major human pathogen, and a leading cause of disease and death worldwide. Pneumococcal invasive disease is triggered by initial asymptomatic colonization of the human upper respiratory tract. The pneumococcal serine-rich repeat protein (PsrP) is a lung-specific virulence factor whose functional binding region (BR) binds to keratin-10 (KRT10) and promotes pneumococcal biofilm formation through self-oligomerization. We present the crystal structure of the KRT10-binding domain of PsrP (BR187-385) determined to 2.0 A resolution. BR187-385 adopts a novel variant of the DEv-IgG fold, typical for microbial surface components recognizing adhesive matrix molecules adhesins, despite very low sequence identity. An extended beta-sheet on one side of the compressed, two-sided barrel presents a basic groove that possibly binds to the acidic helical rod domain of KRT10. Our study also demonstrates the importance of the other side of the barrel, formed by extensive well-ordered loops and stabilized by short beta-strands, for interaction with KRT10.
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| - | The basic keratin 10-binding domain of the virulence-associated pneumococcal serine-rich protein PsrP adopts a novel MSCRAMM fold.,Schulte T, Lofling J, Mikaelsson C, Kikhney A, Hentrich K, Diamante A, Ebel C, Normark S, Svergun D, Henriques-Normark B, Achour A Open Biol. 2014 Jan 15;4(1):130090. doi: 10.1098/rsob.130090. PMID:24430336<ref>PMID:24430336</ref> | + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| - | <div class="pdbe-citations 3zgh" style="background-color:#fffaf0;"></div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Strpn]] | + | [[Category: Large Structures]] |
| - | [[Category: Achour, A]] | + | [[Category: Streptococcus pneumoniae TIGR4]] |
| - | [[Category: Diamante, A]] | + | [[Category: Achour A]] |
| - | [[Category: Ebel, C]] | + | [[Category: Diamante A]] |
| - | [[Category: Henriques-Normark, B]] | + | [[Category: Ebel C]] |
| - | [[Category: Hentrich, K]] | + | [[Category: Henriques-Normark B]] |
| - | [[Category: Kikhney, A]] | + | [[Category: Hentrich K]] |
| - | [[Category: Loefling, J]] | + | [[Category: Kikhney A]] |
| - | [[Category: Mikaelsson, C]] | + | [[Category: Loefling J]] |
| - | [[Category: Normark, S]] | + | [[Category: Mikaelsson C]] |
| - | [[Category: Schulte, T]] | + | [[Category: Normark S]] |
| - | [[Category: Svergun, D]] | + | [[Category: Schulte T]] |
| - | [[Category: Keratin-10]]
| + | [[Category: Svergun D]] |
| - | [[Category: Mscramm]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| Structural highlights
Function
PSRP_STRPN Protein that allows bacteria to adhere to mammalian host cells. Required for full virulence in mouse infection models when infected intranasally (PubMed:16861665). Required for adhesion to host cells in vitro and for persistence in the lower respiratory tract (PubMed:18507531). Binds host keratin 10 (KRT10) on lung cells which mediates adhesion via the C-terminus of the basic region (BR, residues 273-341); glycosylation of either protein is not required for the interaction (PubMed:19627498). A region in the N-terminus (residues 122-166) self aggregates, contributing to mature biofilm formation (PubMed:20714350). The basic region (BR, residues 187-385) also self aggregates; the BR binds DNA which enhances self aggregation (PubMed:27582320).[1] [2] [3] [4] [5]
References
- ↑ Obert C, Sublett J, Kaushal D, Hinojosa E, Barton T, Tuomanen EI, Orihuela CJ. Identification of a Candidate Streptococcus pneumoniae core genome and regions of diversity correlated with invasive pneumococcal disease. Infect Immun. 2006 Aug;74(8):4766-77. PMID:16861665 doi:10.1128/IAI.00316-06
- ↑ Rose L, Shivshankar P, Hinojosa E, Rodriguez A, Sanchez CJ, Orihuela CJ. Antibodies against PsrP, a novel Streptococcus pneumoniae adhesin, block adhesion and protect mice against pneumococcal challenge. J Infect Dis. 2008 Aug 1;198(3):375-83. PMID:18507531 doi:10.1086/589775
- ↑ Shivshankar P, Sanchez C, Rose LF, Orihuela CJ. The Streptococcus pneumoniae adhesin PsrP binds to Keratin 10 on lung cells. Mol Microbiol. 2009 Aug;73(4):663-79. PMID:19627498 doi:10.1111/j.1365-2958.2009.06796.x
- ↑ Sanchez CJ, Shivshankar P, Stol K, Trakhtenbroit S, Sullam PM, Sauer K, Hermans PW, Orihuela CJ. The pneumococcal serine-rich repeat protein is an intra-species bacterial adhesin that promotes bacterial aggregation in vivo and in biofilms. PLoS Pathog. 2010 Aug 12;6(8):e1001044. PMID:20714350 doi:10.1371/journal.ppat.1001044
- ↑ Schulte T, Mikaelsson C, Beaussart A, Kikhney A, Deshmukh M, Wolniak S, Pathak A, Ebel C, Lofling J, Fogolari F, Henriques-Normark B, Dufrene YF, Svergun D, Nygren PA, Achour A. The BR domain of PsrP interacts with extracellular DNA to promote bacterial aggregation; structural insights into pneumococcal biofilm formation. Sci Rep. 2016 Sep 1;6:32371. doi: 10.1038/srep32371. PMID:27582320 doi:http://dx.doi.org/10.1038/srep32371
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