3zgi

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Crystal structure of the KRT10-binding region domain of the pneumococcal serine rich repeat protein PsrPCrystal structure of the KRT10-binding region domain of the pneumococcal serine rich repeat protein PsrP

Structural highlights

3zgi is a 3 chain structure with sequence from Streptococcus pneumoniae TIGR4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.25Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

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.

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[6]

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

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ Schulte T, Lofling J, Mikaelsson C, Kikhney A, Hentrich K, Diamante A, Ebel C, Normark S, Svergun D, Henriques-Normark B, Achour A. The basic keratin 10-binding domain of the virulence-associated pneumococcal serine-rich protein PsrP adopts a novel MSCRAMM fold. Open Biol. 2014 Jan 15;4(1):130090. doi: 10.1098/rsob.130090. PMID:24430336 doi:http://dx.doi.org/10.1098/rsob.130090

3zgi, resolution 2.25Å

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