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Pore‐forming toxins with built‐in triggers and switches
Author(s) -
Bayley
Publication year - 1998
Publication title -
journal of applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 156
eISSN - 1365-2672
pISSN - 1364-5072
DOI - 10.1046/j.1365-2672.1998.0840s1151s.x-i2
Subject(s) - homomeric , protein engineering , mutagenesis , chemistry , covalent bond , chemical modification , analyte , biophysics , combinatorial chemistry , biochemistry , enzyme , biology , mutation , organic chemistry , protein subunit , gene
Pore‐forming proteins are being engineered to produce new components for biomolecular materials and devices. The primary target of these studies has been staphylococcal α‐haemolysin, which is a 293 amino acid, water soluble polypeptide that self assembles in lipid bilayers to form heptameric pores of 1–2 nm internal diameter. By genetic engineering and targeted chemical modification, we have produced α‐haemolysins in which pore activity can be triggered or switched on and off by biochemical, chemical or physical stimuli, including the action of enzymes, non‐covalent and covalent modification, and irradiation with near UV light. One application is in sensor technology. The remodelled molecules can be used as components of sensitive, selective, real‐time sensors for the stimuli that affect their activities, as demon strated with divalent metal ions as analyte. Now, we are using combinatorial mutagenesis and DNA shuffling, as well as structure‐based approaches, to generate homomeric and heteromeric pores with high affinity binding sites for additional analytes.