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Positive functional synergy of structurally integrated artificial protein dimers assembled by Click chemistry

DOI: 10.1038/s42004-019-0185-5 DOI Help

Authors: Harley L. Worthy (Cardiff University) , Husam Sabah Auhim (Cardiff University; Baghdad University) , W. David Jamieson (Cardiff University) , Jacob R. Pope (Cardiff University) , Aaron Wall (Cardiff University) , Robert Batchelor (Cardiff University) , Rachel L. Johnson (Cardiff University) , Daniel W. Watkins (Cardiff University; University of Bristol) , Pierre Rizkallah (Cardiff University) , Oliver K. Castell (Cardiff University) , D. Dafydd Jones (Cardiff University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Communications Chemistry , VOL 2

State: Published (Approved)
Published: July 2019
Diamond Proposal Number(s): 14843

Open Access Open Access

Abstract: Construction of artificial higher order protein complexes allows sampling of structural architectures and functional features not accessible by classical monomeric proteins. Here, we combine in silico modelling with expanded genetic code facilitated strain promoted azide-alkyne cycloaddition to construct artificial complexes that are structurally integrated protein dimers and demonstrate functional synergy. Using fluorescent proteins sfGFP and Venus as models, homodimers and heterodimers are constructed that switched ON once assembled and display enhanced spectral properties. Symmetrical crosslinks are found to be important for functional enhancement. The determined molecular structure of one artificial dimer shows that a new long-range polar network comprised mostly of organised water molecules links the two chromophores leading to activation and functional enhancement. Single molecule analysis reveals the dimer is more resistant to photobleaching spending longer times in the ON state. Thus, genetically encoded bioorthogonal chemistry can be used to generate truly integrated artificial protein complexes that enhance function.

Journal Keywords: Chemical modification; Protein design; Self-assembly; Synthetic biology

Subject Areas: Chemistry

Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography


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