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SUMMARY:Expanding the universe of protein structure and function by design
  - Dek Woolfson Schools of Chemistry and Biochemistry\, &amp\; BrisSynBio 
 University of Bristol\, UK
DTSTART:20160518T093000Z
DTEND:20160518T103000Z
UID:TALK66268@talks.cam.ac.uk
CONTACT:Jerome Charmet
DESCRIPTION:This talk will describe how we have developed an understanding
  of natural protein-folding motif\, namely the alpha-helical coiled-coil t
 hat directs protein oligomerization\; and then how we can apply this knowl
 edge in rational peptide and protein design.  For the latter\, it is now c
 lear that nature has almost certainly only shown us a glimpse of what is p
 ossible structurally and functionally with polypeptide chains.  To help us
  explore past the confines of natural coiled-coil structures\, and into wh
 at has been termed the dark matter of protein space\, we have developed a 
 toolkit of de novo coiled-coil peptides (1). These can be used as building
  blocks for the rapid construction of new protein structures and assemblie
 s. The talk will demonstrate the utility of this approach to make water-so
 luble protein-like barrels and pores (2\, 3)\, which can be engineered to 
 bind biological molecules and catalyse simple reactions (4\, 5).  More rec
 ently we have engineered membrane-spanning variants of these alpha-helical
  barrels\, and in collaboration with Hagan Bayley’s lab\, we have shown 
 that these insert into lipid bilayers and conduct ions in voltage-dependen
 t manners.  The insertion and orientation of peptides into the membranes c
 an be directed by design\, and the channel activities can be controlled th
 rough mutagenesis and blocking reagents.\n\n1.	A Basis Set of de Novo Coil
 ed-Coil Peptide Oligomers for Rational Protein Design and Synthetic Biolog
 y\nJM Fletcher\, AL Boyle\, M Bruning\, GJ Bartlett\, TL Vincent\, NR Zacc
 ai\, CT Armstrong\, EHC Bromley\, PJ Booth\, RL Brady\, AR Thomson\, and D
 N Woolfson\nACS Synthetic Biology 6\, 240-250 (2012)\n\n2.	A de novo pepti
 de hexamer with a mutable channel\nNR Zaccai\, B Chi\, AR Thomson\, AL Boy
 le\, GJ Bartlett\, M Bruning\, N Linden\, RB Sessions\, PJ Booth\, RL Brad
 y and DN Woolfson\nNature Chemical Biology 7\, 935-941 (2011)\n\n3.	Comput
 ational design of water-soluble alpha-helical barrels\nAR Thomson\, CW Woo
 d\, AJ Burton\, GJ Bartlett\, RB Sessions\, RL Brady and DN Woolfson\nScie
 nce 346\, 485-488 (2014)\n\n4.	Accessibility\, Reactivity\, and Selectivit
 y of Side Chains within a Channel of de Novo Peptide Assembly AJ Burton\, 
 F Thomas\, C Agnew\, KL Hudson\, SE Halford\, RL Brady and DN Woolfson\nJ 
 Am Chem Soc 135\, 12524-12527 (2013).\n\n5.	Modular Design of Self-Assembl
 ing Peptide-Based Nanotubes.\nNC Burgess\, TH Sharp\, F Thomas\, CW Wood\,
  AR Thomson\, NR Zaccai\, RL Brady\, LC Serpell and DN Woolfson\nJ Am Chem
  Soc 137\, 10554-10562 (2015).
LOCATION:Department of Chemistry\, Cambridge\, Unilever lecture theatre
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