Influence of the Interdomain Interface on Structural and Redox Properties of Multiheme Proteins

Fangfang Zhong, Therese Albert, Pierre Moënne-Loccoz, Ekaterina V. Pletneva

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Multiheme proteins are important in energy conversion and biogeochemical cycles of nitrogen and sulfur. A diheme cytochrome c4(c4) was used as a model to elucidate roles of the interdomain interface on properties of iron centers in its hemes A and B. Isolated monoheme domains c4-A and c4-B, together with the full-length diheme c4and its Met-to-His ligand variants, were characterized by a variety of spectroscopic and stability measurements. In both isolated domains, the heme iron is Met/His-ligated at pH 5.0, as in the full-length c4, but becomes His/His-ligated in c4-B at higher pH. Intradomain contacts in c4-A are minimally affected by the separation of c4-A and c4-B domains, and isolated c4-A is folded. In contrast, the isolated c4-B is partially unfolded, and the interface with c4-A guides folding of this domain. The c4-A and c4-B domains have the propensity to interact even without the polypeptide linker. Thermodynamic cycles have revealed properties of monomeric folded isolated domains, suggesting that ferrous (FeII), but not ferric (FeIII) c4-A and c4-B, is stabilized by the interface. This study illustrates the effects of the interface on tuning structural and redox properties of multiheme proteins and enriches our understanding of redox-dependent complexation.

Original languageEnglish (US)
Pages (from-to)20949-20963
Number of pages15
JournalInorganic Chemistry
Issue number51
StatePublished - Dec 26 2022
Externally publishedYes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry


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