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

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 Co^II-chaperone for vitamin B₁₂. Upon binding nucleotide (GTP) and Mg^II, CobW assembles a high-affinity site that can obtain Co^II or Zn^II from the intracellular milieu. In idealised cells with sensors at the mid-points of their responses, competition within the cytosol enables Co^II to

SUBMITTER: Young TR 

PROVIDER: S-EPMC7895991 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature