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Structural basis for the role of serine-rich repeat proteins from Lactobacillus reuteri in gut microbe–host interactions

DOI: 10.1073/pnas.1715016115 DOI Help

Authors: Saannya Sequeira (University of East Anglia) , Devon Kavanaugh (Quadram Bioscience Institute) , Donald A. Mackenzie (Quadram Bioscience Institute) , Tanja Šuligoj (Quadram Bioscience Institute) , Samuel Walpole (University of East Anglia) , Charlotte Leclaire (Quadram Bioscience Institute) , A. Patrick Gunning (Quadram Bioscience Institute) , Dimitrios Latousakis (Quadram Bioscience Institute) , William G. T. Willats (Newcastle University) , Jesus Angulo (University of East Anglia) , Changjiang Dong (University of East Anglia) , Nathalie Juge (Quadram Bioscience Institute)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 404

State: Published (Approved)
Published: March 2018
Diamond Proposal Number(s): 9475

Open Access Open Access

Abstract: Lactobacillus reuteri, a Gram-positive bacterial species inhabiting the gastrointestinal tract of vertebrates, displays remarkable host adaptation. Previous mutational analyses of rodent strain L. reuteri 100-23C identified a gene encoding a predicted surface-exposed serine-rich repeat protein (SRRP100-23) that was vital for L. reuteri biofilm formation in mice. SRRPs have emerged as an important group of surface proteins on many pathogens, but no structural information is available in commensal bacteria. Here we report the 2.00-Å and 1.92-Å crystal structures of the binding regions (BRs) of SRRP100-23 and SRRP53608 from L. reuteri ATCC 53608, revealing a unique β-solenoid fold in this important adhesin family. SRRP53608-BR bound to host epithelial cells and DNA at neutral pH and recognized polygalacturonic acid (PGA), rhamnogalacturonan I, or chondroitin sulfate A at acidic pH. Mutagenesis confirmed the role of the BR putative binding site in the interaction of SRRP53608-BR with PGA. Long molecular dynamics simulations showed that SRRP53608-BR undergoes a pH-dependent conformational change. Together, these findings provide mechanistic insights into the role of SRRPs in host–microbe interactions and open avenues of research into the use of biofilm-forming probiotics against clinically important pathogens.

Journal Keywords: SRRP; Lactobacillus reuteri; adhesin; biofilm; mucin

Diamond Keywords: Bacteria; Gut Microbiota

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography

Added On: 19/03/2018 13:59


Discipline Tags:

Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)