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SUMMARY:Structural elucidation of the self-assembly mechanism of amyloid f
 ibrils - Sheena Radford\, University of Leeds
DTSTART:20090225T110000Z
DTEND:20090225T120000Z
UID:TALK14133@talks.cam.ac.uk
CONTACT:8272
DESCRIPTION:Understanding how different proteins assemble into the ordered
 \, insoluble aggregates associated with amyloid disease is a formidable ch
 allenge. Whilst it is generally accepted that protein unfolding is require
 d for the formation of amyloid fibrils from natively folded proteins in vi
 tro and\, therefore\, presumably also in vivo\, the point at which the fol
 ding and aggregation free energy landscapes diverge\, and the role of diff
 erent amino acid residues in determining folding versus aggregation\, rema
 in obscure. We have attempted to address this question by determining the 
 mechanisms of protein folding and aggregation of the naturally amyloidogen
 ic protein\, beta-2-microglobulin\, under different solution conditions Us
 ing NMR the conformational properties of species that initiate the amyloid
  cascade have been identified and an array of mutants have been created to
  explore the role of individual residues in governing the rates of aggrega
 tion.  Even more challenging\, however\, is the identification of early ol
 igomeric species and their structural characterisation\, since such specie
 s are aggregation-prone\, short-lived and rapidly equilibrating.  Using an
  array of different biophysical methods and approaches\, our aim is to elu
 cidate the mechanism of amyloid formation of this protein in atomistic det
 ail\, so as to provide new fundamental understandings of protein-protein r
 ecognition in amyloid assembly that may help to pave the way towards thera
 peutic intervention.
LOCATION:Unilever Lecture Theatre\, Unilever Centre\, Department of Chemis
 try
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