Calculating metalation in cells reveals CobW acquires CoII for vitamin B12 biosynthesis upon binding nucleotide

Tessa R. Young, Maria Alessandra Martini, Deenah Osman, Richard J. Morton, Evelyne Deery, Martin J. Warren, Nigel J. Robinson

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Received Date: 26th May 20

Protein metal-occupancy (metalation) in vivo has been elusive. Here we develop a metalation-calculator which accounts for inter-metal competition and changing metal-availabilities inside cells. The calculations are based on available free-energies of metals determined from the responses of metal sensors. We use the calculator to understand the function and mechanism of CobW, a predicted CoII-chaperone for vitamin B12. CobW is calculated to acquire negligible metal alone: But, 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 reveals how CobW acquires its metal and is made available for use with other proteins.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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