Issue 26, 2025, Issue in Progress

Increased functional unit flexibility and solvent accessibility favours oxygen capture in molluscan hemocyanin

Abstract

Hemocyanins are a class of copper-based oxygen transport proteins, widely studied for their unique oxygen-binding processes and their role in the molluscan immune response. In this study, we utilised computational simulations to investigate the first functional unit (FU-a) of Crepidula fornicata (slipper limpet) hemocyanin, a member of the keyhole limpet hemocyanin family. Using quantum mechanics/molecular mechanics (QM/MM) methods, we designed oxygenated and deoxygenated models of FU-a and conducted molecular dynamics simulations to explore their functional dynamics and oxygen accessibility. We specifically focused on understanding the global and localised dynamics between the two conformational states. By employing principal component analysis (PCA) and modevector analysis, we differentiated the dynamic properties of the deoxygenated and oxygenated states of the hemocyanin. Furthermore, we explored the impact of oxygenation on hydration and tunnel cavity formation. Our results reveal that oxygen entry is mediated by a single bidirectional tunnel, with its permeability tightly regulated by differential histidine-based copper coordination. Importantly, we identified Glu352 as an evolutionary conserved molecular “shutter,” whose conformational changes govern the opening and closure of this tunnel. These findings provide insight into the mechanistic regulation of oxygen transport in molluscan hemocyanins, with implications for understanding their functional versatility and potential applications.

Graphical abstract: Increased functional unit flexibility and solvent accessibility favours oxygen capture in molluscan hemocyanin

Supplementary files

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Article information

Article type
Paper
Submitted
08 May 2025
Accepted
06 Jun 2025
First published
16 Jun 2025
This article is Open Access
Creative Commons BY license

RSC Adv., 2025,15, 20373-20384

Increased functional unit flexibility and solvent accessibility favours oxygen capture in molluscan hemocyanin

J. G. Davies, J. A. Platts, M. T. Young and G. E. Menzies, RSC Adv., 2025, 15, 20373 DOI: 10.1039/D5RA03248B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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