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SUMMARY:How to Fold Every Protein: (Mission Accomplished?) - Stephen D Fri
 ed\, John Hopkins University
DTSTART:20241211T140000Z
DTEND:20241211T150000Z
UID:TALK218719@talks.cam.ac.uk
CONTACT:Kate Davenport
DESCRIPTION:Recent advances in artificial intelligence have addressed a lo
 ng-standing question in protein biophysics: What is the relationship betwe
 en a protein’s primary sequence and its native three-dimensional structu
 re?  On the other hand\, the process by which proteins navigate to these n
 ative states during their biosynthesis or following their denaturation is 
 perilous\, complex\, and much less predictable.  Many proteins misfold\, a
  process which can sometimes be reverted through chaperones\, but which is
  also associated with a wide range of ailments\, particularly neurodegener
 ative diseases.  We became interested in delineating which (kinds of) prot
 eins are capable of refolding into their native conformations spontaneousl
 y versus which ones require chaperone assistance.  To do so\, we developed
  limited proteolysis mass spectrometry (LiP-MS) methods\, a structural pro
 teomic approach that can interrogate protein conformation and misfolding o
 n the proteome scale.  These experiments provide a holistic view of what p
 roperties facilitate refoldability and have highlighted an important and u
 nexpected role for intrinsically disordered regions.  I will also highligh
 t a more recent study wherein we discovered a link between nonrefoldabilit
 y and cognitive decline\, by using LiP-MS to compare hippocampal proteins 
 in old rats that have impaired cognition to those from age-matched animals
  that retain their spatial memory.   These experiments uncover several hun
 dred proteins that endure cognition-associated structural changes (CASCs)\
 , and provide evidence that the intersection between protein misfolding an
 d age-related neurological disease expands beyond a small number of amyloi
 d-forming proteins.
LOCATION:CRUK CI Lecture Theatre
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