Structure of RagB, a major immunodominant outer‐membrane surface receptor antigen of Porphyromonas gingivalis. (16th November 2015)

• Record Type: Journal Article
• Authors: Goulas, T.; Garcia‐Ferrer, I.; Hutcherson, J.A.; Potempa, B.A.; Potempa, J.; Scott, D.A.; Xavier Gomis‐Rüth, F.
• Is Part Of: Molecular oral microbiology. Volume 31:Number 6(2016:Dec.)
• Page Start: 472
• Page End: 485
• Publication Date: 2015-11-16
• Subjects: periodontitis -- sugar‐binding proteins -- SusD‐like proteins -- tetratricorepeat proteins -- X‐ray crystal structure; Mouth -- Microbiology -- Periodicals; Respiratory infections -- Microbiology -- Periodicals; Mouth -- Diseases -- Immunological aspects -- Periodicals; 617.522
• DOI: 10.1111/omi.12140
• Languages: English
• ISSNs: 2041-1006

Abstract

Summary: Porphyromonas gingivalis is the main causative agent of periodontitis. It deregulates the inflammatory and innate host immune responses through virulence factors, which include the immunodominant outer‐membrane surface receptor antigens A ( Pg RagA) and B ( Pg RagB), co‐transcribed from the rag pathogenicity island. The former is predicted to be a Ton‐dependent porin‐type translocator but the targets of this translocation and the molecular function of Pg RagB are unknown. Phenomenologically, Pg RagB has been linked with epithelial cell invasion and virulence according to murine models. It also acts as a Toll‐like receptor agonist and promotes multiple mediators of inflammation. Hence, Pg RagB is a candidate for the development of a periodontitis vaccine, which would be facilitated by the knowledge of its atomic structure. Here, we crystallized and solved the structure of 54‐kDa Pg RagB, which revealed a single domain centered on a curved helical scaffold. It consists of four tetratrico peptide repeats (TPR1–4), each arranged as two helices connected by a linker, plus two extra downstream capping helices. The concave surface bears four large intertwined irregular inserts (A–D), which contribute to an overall compact moiety. Overall, Pg RagB shows substantial structural similarity with Bacteroides thetaiotaomicron SusD and Tannerella forsythia NanU, which are, respectively, engaged in binding and uptake of malto‐oligosaccharide/starch and sialic acid. This suggests a similar sugar‐binding function for Pg RagB for uptake by the cognate Pg RagA translocator, and, consistently, three potential monosaccharide‐binding sites were tentatively assigned on the molecular surface.