Basset, AlanZhang, FanBenes, CyrilSayeed, SabinaHerd, MurielThompson, ClaudetteGolenbock, Douglas T.Camilli, AndrewMalley, Richard2022-08-232022-08-232013-01-252018-03-15<p>J Biol Chem. 2013 Jan 25;288(4):2665-75. doi: 10.1074/jbc.M112.398875. Epub 2012 Dec 11. <a href="https://doi.org/10.1074/jbc.M112.398875">Link to article on publisher's site</a></p>0021-9258 (Linking)10.1074/jbc.M112.39887523233677https://hdl.handle.net/20.500.14038/35155The pneumococcal type 1 pilus is an inflammatory and adherence-promoting structure associated with increased virulence in mouse models. We show that RrgA, an ancillary pilus subunit devoid of a lipidation motif, particularly when presented as part of an oligomer, is a TLR2 agonist. The surface-exposed domain III, and in particular a 49-amino acid sequence (P3), of the protein is responsible for the TLR2 activity of RrgA. A pneumococcal mutant carrying RrgA with a deletion of the P3 region was significantly reduced in its ability to activate TLR2 and induce TNF-alpha responses after mouse intraperitoneal infection, whereas no such difference could be noted when TLR2(-/-) mice were challenged, further implicating this region in recognition by TLR2. Thus, we conclude that the type 1 pneumococcal pilus can activate cells via TLR2, and the ancillary pilus subunit RrgA is a key component of this activation.en-US© 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Publisher PDF posted after 12 months as allowed by the publisher's author rights policy at https://www.asbmb.org/journals-news/editorial-policies.Bacterial PathogenesisCell Surface ProteinStreptococcusToll-like Receptors (TLR)Virulence FactorsBiochemistry, Biophysics, and Structural BiologyImmunology and Infectious DiseaseInfectious DiseaseJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1369&amp;context=infdis_pp&amp;unstamped=1https://escholarship.umassmed.edu/infdis_pp/36811785995infdis_pp/368