Professor Steve Matthews, Department of Life Sciences, Imperial College London
Tuesday 21st February, 1.00 p.m., Stacey Lecture Theatre 1
Bacterial biofilms are a major cause of recurrent disease, allowing reservoirs of bacteria to persist in a human/animal host or in the external environment. A key component of these biofilms is functional amyloid – robust fibres that contribute to the mechanical properties of biofilm. Knowledge of the molecular properties of the proteins involved in amyloid formation is vital to our understanding of the means by which bacteria target hosts, evade the immune system, survive environmental stresses and cause disease.
There are two genetically distinct functional amyloid systems known in bacteria – the Curli (first characterised in E. coli) and Fap (P. aeruginosa) extracellular fibre systems. Recent breakthroughs have led to the structures of a number of the curli proteins, the first of which was solved in our lab, however the atomic structures of any of the components of the latter are unknown. We present here the high resolution crystal structure of the membrane protein transport component FapF showing that it belongs to a new family of multimeric β-barrel membrane pore that are gated by a helical plug, The structure of FapF is distinct from that of the equivalent membrane component from the curli system, CsgG, which is an ungated nonomeric β-barrel pore, but shares common features with other outermembrane secretions systems. Mutagenesis together with bacterial secretion assays support the structural view of how the FapF pore is activated by engagement with the pre-amyloid cargo and proteolysis. Our work unveils an alternative strategy of how gram negative bacterial transport amyloidogenic substrates across the outer membrane in a controlled manner.