Structural motifs in the early metallation steps of Zn(II) and Cd(II) binding to apo-metallothionein 1a

Korkola, Natalie C.; Stillman, Martin J.

doi:10.1016/j.jinorgbio.2023.112429

Cited by 1 publication

(2 citation statements)

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“…[35] Unfolding apo-βαMT prior to metallation using Zn(II) or Cd(II) results in altered M x S y structures than those found when the apo-βαMT is folded. [49] This work expands this possibility to the metal-loading status and gives further insight into the non-traditional metallation of MTs. These results combined with studies of other metals show insight into how MTs deal with the many essential and xenobiotic metals they may encounter in physiology.…”

Section: Observed Cooperativity and Domain Specificity In Other Metal...mentioning

confidence: 82%

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Bi(III) Binding Stoichiometry and Domain‐Specificity Differences Between Apo and Zn(II)‐bound Human Metallothionein 1a

Korkola,

Ostertag,

Toswell

et al. 2024

Chemistry A European J

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Bismuth is a xenobiotic metal with a high affinity to sulfur that is used in a variety of therapeutic applications. Bi(III) induces the cysteine‐rich metallothionein (MT), a protein known to form two‐domain cluster structures with certain metals such as Zn(II), Cd(II), or Cu(I). The binding of Bi(III) to MTs has been previously studied, but there are conflicting reports on the stoichiometry and binding pathway, which appear to be highly dependent on pH and initial metal‐loading status of the MT. Additionally, domain specificity has not been thoroughly investigated. In this paper, ESI‐MS was used to determine the binding constants of [Bi(EDTA)]‐ binding to apo‐MT1a and its individual αMT fragment. The results were compared to previous experiments using βMT1a and βαMT3. Domain specificity was investigated using proteolysis methods and the initial cooperatively formed Bi2MT was found to bind to cysteines that spanned across the traditional metal binding domain regions. Titrations of [Bi(EDTA)]‐ into Zn7MT were performed and were found to result in a maximum stoichiometry of Bi7MT, contrasting the Bi6MT formed when [Bi(EDTA)]‐ was added to apo‐MT. These results show that the initial structure of the apo‐MT determines the stoichiometry of new incoming metals and explains the previously observed differences in stoichiometry.

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Section: Observed Cooperativity and Domain Specificity In Other Metal...mentioning

confidence: 82%

“…Unfolding the apo‐βMT using GdmCl resulted in more favourable formation of Bi 3 βMT compared to apo‐βMT under native conditions [35] . Unfolding apo‐βαMT prior to metallation using Zn(II) or Cd(II) results in altered M x S y structures than those found when the apo‐βαMT is folded [49] …”

Section: Resultsmentioning

confidence: 98%