TY - JOUR
T1 - Influence of the Interdomain Interface on Structural and Redox Properties of Multiheme Proteins
AU - Zhong, Fangfang
AU - Albert, Therese
AU - Moënne-Loccoz, Pierre
AU - Pletneva, Ekaterina V.
N1 - Funding Information:
This work was supported by NIH grants R01-GM098502 (to E.V.P.) and P20-GM113132 (COBRE Institute for Biomolecular targeting at Dartmouth). We thank Yunling Deng for help with analyses of acidic titration of Ps c , Michael J. Ragusa for insights about properties of the c -A dimer, and Jiaqi Zhu for assistance with making heat maps. 4 4
Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/12/26
Y1 - 2022/12/26
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.inorgchem.2c03427
DO - 10.1021/acs.inorgchem.2c03427
M3 - Article
C2 - 36493379
AN - SCOPUS:85143856416
SN - 0020-1669
VL - 61
SP - 20949
EP - 20963
JO - Inorganic Chemistry
JF - Inorganic Chemistry
IS - 51
ER -