Unusual structural features of streptococcal surface proteins and implications for function Event as iCalendar

(Biodiversity and Biosecurity, Biological Sciences, Seminars)

24 October 2017

1 - 2pm

Venue: Biology Building, MAC 1

Location: 5 Symonds Street, Auckland

Host: School of Biological Sciences

Contact info: Professor Christopher Squire

Contact email: c.squire@auckland.ac.nz

Dr Uli Schwarz-Linek, School of Biology, University of St Andrews, UK

The multiple and often serotype-specific functions of M proteins are generally poorly understood in molecular terms, arguably due to a lack of structural information. All available evidence supports the idea of M proteins adopting an elongated dimeric, parallel coiled-coil conformation. This makes M proteins difficult targets for conventional structural biology.

Dr Uli Schwarz-Linek and colleagues combined EPR and NMR spectroscopy to map the hypervariable region (HVR) in full length M3 protein in solution and derive a structural model. They found that M3-HVR forms a well-defined folded structure that deviates from coiled coil topology. This fold presents collagen-binding motifs associated with rheumatic fever in a structural context that depends on the dimeric state of the protein and is required for binding activity. Using triple-helical peptide libraries Dr Schwarz-Linek and his colleagues identified M3-binding regions within the triple-helical domain of collagen II. The M protein:collagen interaction was found to mediate biofilm formation of M3 clinical isolates.

Their study reveals a surprising structural complexity of the M3 protein with implications for its function in rheumatic fever and biofilms. It also suggests that M proteins may be structurally more diverse than assumed.