5jui
domain-swapped dimer of the the KRT10-binding region (BR) of PsrP
Structural highlights
FunctionPSRP_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 PubMedThe major human pathogen Streptococcus pneumoniae is a leading cause of disease and death worldwide. Pneumococcal biofilm formation within the nasopharynx leads to long-term colonization and persistence within the host. We have previously demonstrated that the capsular surface-associated pneumococcal serine rich repeat protein (PsrP), key factor for biofilm formation, binds to keratin-10 (KRT10) through its microbial surface component recognizing adhesive matrix molecule (MSCRAMM)-related globular binding region domain (BR187-385). Here, we show that BR187-385 also binds to DNA, as demonstrated by electrophoretic mobility shift assays and size exclusion chromatography. Further, heterologous expression of BR187-378 or the longer BR120-378 construct on the surface of a Gram-positive model host bacterium resulted in the formation of cellular aggregates that was significantly enhanced in the presence of DNA. Crystal structure analyses revealed the formation of BR187-385 homo-dimers via an intermolecular beta-sheet, resulting in a positively charged concave surface, shaped to accommodate the acidic helical DNA structure. Furthermore, small angle X-ray scattering and circular dichroism studies indicate that the aggregate-enhancing N-terminal region of BR120-166 adopts an extended, non-globular structure. Altogether, our results suggest that PsrP adheres to extracellular DNA in the biofilm matrix and thus promotes pneumococcal biofilm formation. The BR domain of PsrP interacts with extracellular DNA to promote bacterial aggregation; structural insights into pneumococcal biofilm formation.,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 Sci Rep. 2016 Sep 1;6:32371. doi: 10.1038/srep32371. PMID:27582320[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
