Oral Presentation The 47th Lorne Conference on Protein Structure and Function 2022

 ‘Periscope Proteins’ at the host:microbe interface (#10)

Fiona Whelan 1 , Aleix Lafita 2 , Alex Bateman 2 , Jennifer R Potts 3
  1. Department of Molecular and Biomedical Science, School of Biological Sciences, University of Adelaide, SA, Australia
  2. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, CB10 1SD, United Kingdom
  3. School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia

Gram-positive bacteria attach proteins to the cell surface to mediate interactions critical to bacterial virulence, facilitating host cell adhesion, attachment to prosthetic devices, and homotypic interactions in protein-dependent biofilm. The cell surface is a spatially competitive space, driving evolution of unusual protein folds to facilitate functional domain exposure. High-identity repeats are a characteristic feature of a group of adhesive protein structures. Through structural and biophysical analyses, we have revealed the structure of three such monomeric surface proteins from Gram-positive bacteria. In repetitive contexts, we determined these monomeric repeats can form rod-like highly anisotropic structures on the nanometer scale, demonstrating an elegant solution to the display of functional domains at the host:microbe interface. Long-read sequencing from the Public Health England NCTC3000 data set identifies repeat domain topology in >1,500 proteins from Gram-positive and Gram-negative bacteria, with >50 featuring strain-dependent variation in repeat number. Combining the observed repeat number variation with the characterization of linearly extended rod-like topologies, we have named this group ‘Periscope Proteins’, revealing a widespread mechanism of surface variation in bacteria [1].

 

  1. Whelan F. et al., Periscope Proteins are variable-length regulators of bacterial cell surface interactions PNAS, Jun 2021, 118 (23) e2101349118; DOI: 10.1073/pnas.2101349118.