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SUMMARY:Structure and antigenicity of amyloid fibrils - Marcus Fandrich
DTSTART:20071211T103000Z
DTEND:20071211T113000Z
UID:TALK9337@talks.cam.ac.uk
CONTACT:Giorgio Favrin
DESCRIPTION:This presentation will focus mainly on the structural analysis
  of amyloid fibrils with cryo microscopy and on the generation and charact
 erisation of a conformation-sensitive antibody domain.\n\n(1) Previously\,
  cryo microscopy yielded for one morphology of an Alzheimer's Aβ(1-40) am
 yloid fibril a density map at 26 Å resolution [Sachse et al. J. Mol. Biol
 . 362\, 347f. (2006)]. More recently\, we have explored the structural het
 erogeneity of different Aβ(1-40) amyloid fibrils in more detail and obtai
 ned\, for one fibril morphology\, a structural resolution of less than 10 
 Å. For this fibril we could determine the packing of the β-sheet structu
 re and its protofilament organisation. The observed structure differs sign
 ificantly from previous proposals on the protofilament-protofilament inter
 actions of amyloid fibrils in Alzheimer's disease. By contrast\, it is sim
 ilar to recently described steric zipper structures [Sawaya et al. Nature 
 447\, 453-457 (2007)]. \n\n(2) We have generated an antibody domain\, term
 ed B10\, that recognizes an amyloid-specific and conformationally defined 
 epitope [Habicht et al. PNAS 104\, 19232–7\, (2007)]. This antibody doma
 in was selected by phage-display from a recombinant library of camelid ant
 ibody domains. Surface plasmon resonance\, immunoblots and immunohistochem
 istry show that this antibody domain distinguishes Aβ amyloid fibrils fro
 m disaggregated Aβ peptide as well as from specific Aβ oligomers. The an
 tibody domain possesses functional activity in preventing the formation of
  mature amyloid fibrils by stabilizing Aβ protofibrils. These data sugges
 t possible applications of B10 in the detection of amyloid fibrils or in t
 he modulation of their formation.\n\n\n\n
LOCATION:Todd Hamied Room\,  Department of Chemistry
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