Post-translational insertion of boron in proteins to probe and modulate function.


Journal

Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976

Informations de publication

Date de publication:
12 2021
Historique:
received: 21 01 2021
accepted: 25 08 2021
pubmed: 3 11 2021
medline: 29 12 2021
entrez: 2 11 2021
Statut: ppublish

Résumé

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'.

Identifiants

pubmed: 34725511
doi: 10.1038/s41589-021-00883-7
pii: 10.1038/s41589-021-00883-7
pmc: PMC8604732
doi:

Substances chimiques

Proteins 0
Boron N9E3X5056Q
Alanine OF5P57N2ZX

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1245-1261

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R000255/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P026311/1
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2021. The Author(s).

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Auteurs

Tim A Mollner (TA)

Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.

Patrick G Isenegger (PG)

Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.

Brian Josephson (B)

Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.

Charles Buchanan (C)

Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.

Lukas Lercher (L)

Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.

Daniel Oehlrich (D)

Neuroscience Medicinal Chemistry, Janssen Research and Development, Beerse, Belgium.

D Flemming Hansen (DF)

Division of Biosciences, University College London, London, UK.

Shabaz Mohammed (S)

Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.
Department of Biochemistry, University of Oxford, Oxford, UK.
The Rosalind Franklin Institute, Oxfordshire, Oxford, UK.

Andrew J Baldwin (AJ)

Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK.
The Rosalind Franklin Institute, Oxfordshire, Oxford, UK.

Véronique Gouverneur (V)

Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.

Benjamin G Davis (BG)

Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK. Ben.Davis@rfi.ac.uk.
The Rosalind Franklin Institute, Oxfordshire, Oxford, UK. Ben.Davis@rfi.ac.uk.

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