Unfolding simulations of holomyoglobin from four mammals: identification of intermediates and β-sheet formation from partially unfolded states.
Authors: Dasmeh Pouria, Kepp Kasper P
Journal: PloS one
Summary
# Editorial Summary Myoglobin's unfolding behaviour remains poorly characterised despite its biological importance, particularly in the holo form (with the heme group intact), which differs substantially from the apo form commonly studied in laboratory conditions. Dasmeh and Kepp used molecular dynamics simulations to model thermal unfolding of myoglobin from four mammalian species (sperm whale, pig, horse, and harbour seal) at physiologically relevant temperatures, tracking changes in protein structure, heme retention, and secondary structure loss over nanosecond timescales. Key findings included species-specific differences in stability: terrestrial mammals (pig and horse) showed earlier helix loss at 400 K than the diving sperm whale, whilst heme loss occurred within 1–3.7 nanoseconds at 500 K across all species, with the heme group substantially slowing helix degradation and protecting the D/E and F helices that interact directly with it. The researchers identified discrete unfolding intermediates persisting between 2–11 nanoseconds, distinct from apoMb intermediates in heme-binding regions, and observed unexpected β-sheet formation in partially unfolded states—a phenomenon prevented by heme presence and absent entirely in sperm whale myoglobin. These findings illuminate how cofactor binding stabilises protein architecture and may explain adaptive differences in oxygen-binding protein resilience across species with different metabolic demands and diving physiology, informing understanding of muscle function and oxygen utilisation in equine athletes.
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Practical Takeaways
- •This fundamental protein chemistry research has no direct application to equine clinical practice, farriery, or performance management.
- •Understanding myoglobin thermal stability differences between species is of theoretical interest only and does not inform treatment or management of equine conditions.
- •The study contributes to basic biochemistry knowledge but does not translate to practical recommendations for working with horses.
Key Findings
- •Heme loss occurred within 1.0-3.7 ns at 500 K across four mammalian species, with sperm whale myoglobin showing highest heme retention.
- •Horse and pig myoglobin showed greater helix instability at 400 K compared to sperm whale, suggesting terrestrial species have less stable helical regions.
- •C- and F-helices were lost rapidly in all species, while heme presence delayed overall helix loss and reduced β-sheet formation tendency.
- •Intermediates of holoMb unfolding were identified between 2-11 ns, with structural conservation in A and H helices but substantial differences in heme-interacting D-, E-, and F-helices.