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SUMMARY:Keynote 7\, Prof. Mei Hong: Structure and Dynamics of Amyloid Prot
 eins from Solid-State NMR: Glucagon & Tau
DTSTART;VALUE=DATE-TIME:20191010T120000Z
DTEND;VALUE=DATE-TIME:20191010T124000Z
DTSTAMP;VALUE=DATE-TIME:20260525T152650Z
UID:indico-contribution-140-766@lindico453.srv.lu.se
DESCRIPTION:Speakers: Mei Hong (MIT\, USA)\nProtein misfolding into amyloi
 d fibrils is common not only in neurodegenerative diseases but also in pha
 rmaceutical sciences\, where many peptide-based drugs have the tendency to
  fibrillize\, thus impeding solution formulation of the drug. Using solid-
 state NMR spectroscopy\, we have investigated the structure and dynamics o
 f two amyloid fibrils\, one formed by the peptide hormone glucagon\, which
  is used to treat diabetic hypoglycemia\, and the other formed by the micr
 otubule-binding protein tau\, which is found in many neurodegenerative dis
 eases. The glucagon fibril structure is unique among all amyloid proteins 
 known to date: the -sheet is antiparallel rather than parallel hydrogen
 -bonded\, contains two coexisting molecular conformations in a single ultr
 astructural morphology\, and has an extraordinary -strand length of 10 
 nm. The 1.7 Å resolution structure reveals many stabilizing interactions 
 for the fibril\, thus suggesting future strategies for designing glucagon 
 analogs that resist fibril formation. Compared to glucagon\, the 40 kDa fu
 ll-length four-repeat tau protein forms a much more complex amyloid fibril
 \, with the majority of the protein being dynamically disordered. Using an
  extensive set of multidimensional correlation solid-state NMR techniques\
 , we have determined the repeat domains that constitute the -sheet core
 \, and show that this core has a single molecular conformation. This monom
 orphic nature for an in-vitro tau fibril is fully consistent with the mono
 morphic nature of brain-derived tau fibrils known to date\, suggesting tha
 t in vitro fibrillized tau is a good model for studying in vivo tau fibril
 s. Further\, the segments outside the rigid core\, which appear as a “fu
 zzy coat” in electron micrographs\, are heterogeneously dynamic. The rep
 eats excluded from the rigid core exhibits partial mobility and -sheet 
 character\, while the proline-rich domains undergo large-amplitude anisotr
 opic motions. These results suggest the structure and dynamics of tau in d
 iseases such as progressive supranuclear palsy\, and open the path for des
 igning tau inhibitors and imaging agents.\n\nhttps://lindico453.srv.lu.se/
 event/125/contributions/766/
LOCATION:Kulturen Auditorium
URL:https://lindico453.srv.lu.se/event/125/contributions/766/
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