Intramolecular covalent protein cross-links for protein engineering.

Lead Research Organisation: University of St Andrews
Department Name: Biology

Abstract

During the past decade, three intramolecular covalent cross-links have been found in Gram-positive bacterial surface proteins. These cross-links are internal covalent bonds between the side chains, and confer remarkable properties, and occur with surprising abundance. These cross-link are self-generating, forming within the proteins without the action of any external influence or enzymes. The biological functions of the isopeptide and ester cross-links appear to be conferral of incredible mechanical, chemical and thermal stability, while thioester cross-link function in adhesion to host tissue via formation of a strong covalent bond.
This project aims to exploit these highly unusual bonds for protein engineering. Isopeptide cross-links are currently used in split-isopeptide domains, to create peptide tags for research. The formation of proteins with high stability makes these cross-links a desirable target for engineering. We hope to engineer these bonds into antibodies and other proteins with a use in research and diagnostics. Thioester domains are of interest for the generation of reactive protein tags against specific targets within cells. We aim to use these remarkable properties for engineering a variety of proteins with molecular biology, biotechnology and pharmaceutical applications.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M010996/1 01/10/2015 30/09/2023
1931116 Studentship BB/M010996/1 27/09/2016 30/09/2020 Ethan Clayton