In silico study of cytochrome-C binding to a cardiolipin-containing membrane.

Authors

Alessia Muroni, Fulvio Erba, Leonardo Domenichelli, Luisa Di Paola, Federica Sinibaldi, Giampiero Mei, Almerinda Di Venere, Velia Minicozzi

Published in

European biophysics journal : EBJ. Jul 25, 2025. Epub Jul 25, 2025.

Abstract

Cytochrome C is a key protein involved in electron transport within the mitochondrial respiratory chain and in apoptosis mechanisms. In this work, we provide a detailed theoretical analysis of the binding mechanism between cytochrome-C and a cardiolipin-containing membrane. Molecular dynamics simulations, along with protein contact network and fractal dimension analyses were employed to investigate the structural changes in cytochrome-C during the binding process. Our results suggest that cytochrome-C follows a two-step binding mechanism, starting with a rapid initial interaction, followed by slower conformational rearrangements. We identified two different cytochrome-C conformations at the membrane: a compact, native-like structure and an extended form. The latter, stabilized by Lys72, exhibits a higher binding affinity (≈ 2 kcal/mol) compared to the former. Protein extension also correlates with increased protein-membrane contact and altered heme ring orientation, suggesting that the partial unfolding of cytochrome-C could be crucial for its peroxidase activity and its role in apoptosis. These findings enhance the understanding of the cytochrome-C's membrane interactions and its diverse functions.

PMID:
40715733
Bibliographic data and abstract were imported from PubMed on 28 Jul 2025.

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