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Calculating metalation in cells reveals CobW acquires Co(II) for vitamin B12 biosynthesis while related proteins prefer Zn(II)

Young, TR; Martini, MA; Foster, AW; Glasfeld, A; Osman, D; Morton, RJ; Deery, E; Warren, MJ; Robinson, NJ

Calculating metalation in cells reveals CobW acquires Co(II) for vitamin B12 biosynthesis while related proteins prefer Zn(II) Thumbnail


Authors

MA Martini

AW Foster

A Glasfeld

D Osman

RJ Morton

E Deery

MJ Warren



Abstract

Protein metal-occupancy (metalation) in vivo has been elusive. To address this challenge, the available free energies of metals have recently been determined from the responses of metal sensors. Here, we use these free energy values to develop a metalation-calculator which accounts for inter-metal competition and changing metal-availabilities inside cells. We use the calculator to understand the function and mechanism of GTPase CobW, a predicted CoII-chaperone for vitamin B12. Upon binding nucleotide (GTP) and MgII, CobW assembles a high-affinity site that can obtain CoII or ZnII from the intracellular milieu. In idealised cells with sensors at the mid-points of their responses, competition within the cytosol enables CoII to outcompete ZnII for binding CobW. Thus, CoII is the cognate metal. However, after growth in different [CoII], CoII-occupancy ranges from 10 to 97% which matches CobW-dependent B12 synthesis. The calculator also reveals that related GTPases with comparable ZnII affinities to CobW, preferentially acquire ZnII due to their relatively weaker CoII affinities. The calculator is made available here for use with other proteins.

Citation

Young, T., Martini, M., Foster, A., Glasfeld, A., Osman, D., Morton, R., …Robinson, N. (2021). Calculating metalation in cells reveals CobW acquires Co(II) for vitamin B12 biosynthesis while related proteins prefer Zn(II). Nature Communications, 12, Article 1195. https://doi.org/10.1038/s41467-021-21479-8

Journal Article Type Article
Acceptance Date Jan 25, 2021
Online Publication Date Feb 19, 2021
Publication Date 2021
Deposit Date Feb 19, 2021
Publicly Available Date Feb 23, 2021
Journal Nature Communications
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 12
Article Number 1195
DOI https://doi.org/10.1038/s41467-021-21479-8

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http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/.
© The Author(s) 2021





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