Structure and assembly of the S-layer in C. difficile

DOI: 10.1038/s41467-022-28196-w

Authors: Paola Lanzoni-Mangutchi (Newcastle University) , Oishik Banerji (University of Sheffield) , Jason Wilson (University of Sheffield) , Anna Barwinska-Sendra (Newcastle University) , Joseph A. Kirk (University of Sheffield) , Filipa Vaz (Oslo University Hospital; University of Glasgow) , Shauna O’beirne (University of Sheffield) , Arnaud Basle (Newcastle University) , Kamel El Omari (Diamond Light Source) , Armin Wagner (Diamond Light Source) , Neil F. Fairweather (Imperial College London) , Gillian R. Douce (University of Glasgow) , Per A. Bullough (University of Sheffield) , Robert P. Fagan (University of Sheffield) , Paula Salgado (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 13

State: Published (Approved)
Published: February 2022
Diamond Proposal Number(s): 15523 , 18598 , 19832

Abstract: Many bacteria and archaea possess a two-dimensional protein array, or S-layer, that covers the cell surface and plays crucial roles in cell physiology. Here, we report the crystal structure of SlpA, the main S-layer protein of the bacterial pathogen Clostridioides difficile, and use electron microscopy to study S-layer organisation and assembly. The SlpA crystal lattice mimics S-layer assembly in the cell, through tiling of triangular prisms above the cell wall, interlocked by distinct ridges facing the environment. Strikingly, the array is very compact, with pores of only ~10 Å in diameter, compared to other S-layers (30–100 Å). The surface-exposed flexible ridges are partially dispensable for overall structure and assembly, although a mutant lacking this region becomes susceptible to lysozyme, an important molecule in host defence. Thus, our work gives insights into S-layer organisation and provides a basis for development of C. difficile-specific therapeutics.

Journal Keywords: Bacterial structural biology; Cellular microbiology; Electron microscopy; X-ray crystallography

Diamond Keywords: Bacteria; Gastroenteritis

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: I04-Macromolecular Crystallography , I23-Long wavelength MX , I24-Microfocus Macromolecular Crystallography , Krios III-Titan Krios III at Diamond

Added On: 28/02/2022 11:34

Documents:
s41467-022-28196-w.pdf

Discipline Tags:

Pathogens Antibiotic Resistance Infectious Diseases Health & Wellbeing Biochemistry Chemistry Structural biology Biophysics Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Microscopy Macromolecular Crystallography (MX) Long Wavelength Crystallography Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)