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"Alpha-helical Barrels: Exploring, Understanding and Exploiting a New Class of Protein Structure"

Objective

"Recently through de novo peptide design, we have discovered and presented a new protein structure. This is an all-parallel, 6-helix bundle with a continuous central channel of 0.5 – 0.6 nm diameter. We posit that this is one of a broader class of protein structures that we call the alpha-helical barrels. Here, in three Work Packages, we propose to explore these structures and to develop protein functions within them. First, through a combination of computer-aided design, peptide synthesis and thorough biophysical characterization, we will examine the extents and limits of the alpha-helical-barrel structures. Whilst this is curiosity driven research, it also has practical consequences for the studies that will follow; that is, alpha-helical barrels made from increasing numbers of helices have channels or pores that increase in a predictable way. Second, we will use rational and empirical design approaches to engineer a range of functions within these cavities, including binding capabilities and enzyme-like activities. Finally, and taking the programme into another ambitious area, we will use the alpha-helical barrels to template other folds that are otherwise difficult to design and engineer, notably beta-barrels that insert into membranes to render ion-channel and sensor functions."

Call for proposal

ERC-2013-ADG
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Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

UNIVERSITY OF BRISTOL
Address
Beacon House Queens Road
BS8 1QU Bristol
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 467 844
Principal investigator
Derek Neil Woolfson (Prof.)
Administrative Contact
Audrey Michael (Mrs.)

Beneficiaries (1)

UNIVERSITY OF BRISTOL
United Kingdom
EU contribution
€ 2 467 844
Address
Beacon House Queens Road
BS8 1QU Bristol
Activity type
Higher or Secondary Education Establishments
Principal investigator
Derek Neil Woolfson (Prof.)
Administrative Contact
Audrey Michael (Mrs.)