Projects per year
Abstract
Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α helix buttressed by a polyproline-II helix. PPα-Tyr is water soluble, monomeric, and unfolds cooperatively with a midpoint unfolding temperature (TM) of 39 ˚C. NMR structures of PPα-Tyr reveal proline residues docked between tyrosine side chains as designed. The stability of PPα is sensitive to the aromatic residue: replacing tyrosine by phenylalanine, i.e. changing three solvent-exposed hydroxyl groups to protons, reduces the TM to 20 ˚C. We attribute this to the loss of CH–π interactions between the aromatic and proline rings, which we probe by substituting the aromatic residues with non-proteinogenic side chains. In analyses of natural protein structures we find a preference for proline-tyrosine interactions over other proline-containing pairs, and abundant CH–π interactions in biologically important complexes between proline-rich ligands and SH3 and similar domains.
Original language | English |
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Pages (from-to) | 764-770 |
Number of pages | 7 |
Journal | Nature Chemical Biology |
Volume | 13 |
Issue number | 7 |
Early online date | 22 May 2017 |
DOIs | |
Publication status | Published - 1 Jul 2017 |
Research Groups and Themes
- BrisSynBio
- Bristol BioDesign Institute
- BCS and TECS CDTs
Keywords
- synthetic biology
Fingerprint
Dive into the research topics of 'Engineering protein stability with atomic precision in a monomeric miniprotein'. Together they form a unique fingerprint.Projects
- 3 Finished
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CCP-BioSim: Biomolecular Simulation at the Life Sciences Interface
Mulholland, A. J. (Principal Investigator)
1/07/15 → 30/04/21
Project: Research
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The UK High-End Computing Consortium for Biomolecular Simulation
Mulholland, A. J. (Principal Investigator)
1/11/13 → 31/01/19
Project: Research
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3-month Core Capability for Chemistry Research
Crosby, J. (Principal Investigator)
1/01/13 → 1/04/13
Project: Research
Equipment
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HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities
Alam, S. R. (Manager), Williams, D. A. G. (Manager), Eccleston, P. E. (Manager) & Greene, D. (Manager)
Facility/equipment: Facility
Profiles
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Professor Matthew P Crump
- School of Chemistry - Professor of NMR and Structural Biology
- Cancer
Person: Academic , Member
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Professor Dek N Woolfson
- School of Chemistry - Professor of Chemistry and Biochemistry
- Soft Matter, Colloids and Materials
Person: Academic , Member