Photocontrolled Exposure of Pro-apoptotic Peptide Sequences in LOV Proteins Modulates Bcl-2 Family Interactions.
LOV domains act as biomolecular sensors for light, oxygen or the environment's redox potential. Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen-bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro-apoptotic protein BH3-interacting-domain death agonist (BID). The resulting change in conformation of a flanking amphiphilic α-helix creates a light-dependent optogenetic tool for the modulation of interactions with the anti-apoptotic B-cell leukaemia-2 (Bcl-2) family member Bcl-xL .
School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK.
Robert J
RJ
Mart
School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK.
Dilruba
D
Meah
School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK. allemannrk@cardiff.ac.uk.
Rudolf K
RK
Allemann
D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D005454:Fluorescence Polarization; D055668:Photochemical Processes; D011487:Protein Conformation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry*; D020539:Sequence Analysis, Protein
D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2
apoptosis; photo-uncaging; protein engineering; protein-protein interactions