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The University of Southampton

Structural and mechanistic insight into bacterial amyloid secretion and assembly Seminar

17 October 2018
Building 44, Room 1041 University of Southampton SO17 1BJ

Event details

All welcome at Prof Steve Matthew’s NMR seminar.

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 are known in bacteria – the Curli (first characterised in E. coli) and Fap (Pseudomonas aeruginosa) extracellular fibre systems. Recent breakthroughs have led to new structural and mechanistic insight into curli biogenesis, but the Fap system is poorly understood. We present the high-resolution structure of the membrane protein transport component FapF showing that it belongs to a new family of multimeric β-barrel membrane pore. Combining NMR, X-ray and native MS data we reveal that FapF channel is trimeric and gated by a plug domain, which is regulated by a periplasmic coiled-coil.  These observations are in contrast to those on the equivalent membrane component from the curli system, CsgG - an ungated nonomeric β-barrel pore.  Remarkably, the Fap system does share some features with other outermembrane secretions systems. Mutagenesis together with biological assays and biophysical analysis 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 bacteria transport amyloidogenic substrates across the outer membrane.

Contact details:

Prof Syma Khalid
Dr Phil Williamson

Speaker information

Prof Steve Matthews, Imperial College, London. A major focus of Steve’s group is a better understanding of the interplay between pathogenic organisms, their hosts and the environment, and defining molecular mechanisms relevant to disease.

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