Post-translational insertion of boron in proteins to probe and modulate function
Autor: | Lukas Lercher, Shabaz Mohammed, Tim A. Mollner, Benjamin G. Davis, Patrick G. Isenegger, Brian Josephson, Charles J. Buchanan, Daniel Oehlrich, Andrew Baldwin, Véronique Gouverneur, D. Flemming Hansen |
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Rok vydání: | 2021 |
Předmět: | |
Zdroj: | Nature Chemical Biology |
ISSN: | 1552-4469 1552-4450 |
Popis: | Boron is absent in proteins, yet is a micronutrient. It possesses unique bonding that could expand biological function including modes of Lewis acidity not available to typical elements of life. Here we show that post-translational Cβ–Bγ bond formation provides mild, direct, site-selective access to the minimally sized residue boronoalanine (Bal) in proteins. Precise anchoring of boron within complex biomolecular systems allows dative bond-mediated, site-dependent protein Lewis acid–base-pairing (LABP) by Bal. Dynamic protein-LABP creates tunable inter- and intramolecular ligand–host interactions, while reactive protein-LABP reveals reactively accessible sites through migratory boron-to-oxygen Cβ–Oγ covalent bond formation. These modes of dative bonding can also generate de novo function, such as control of thermo- and proteolytic stability in a target protein, or observation of transient structural features via chemical exchange. These results indicate that controlled insertion of boron facilitates stability modulation, structure determination, de novo binding activities and redox-responsive ‘mutation’. Post-translational site-selective formation of boronoalanine in proteins enables applications of boron for binding partner capture, footprinting of interactions with reactive oxygen species, proteolytic control and mapping of transient structures. |
Databáze: | OpenAIRE |
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