Abstract
Tropomyosin (Tpm) is a continuous α-helical coiled-coil homodimer that regulates actinomyosin interactions in muscle. We examined extended molecular simulations of four Tpms, two from the vertebrate phylum Chordata (rat and pig), and two from the invertebrate Arthropoda (shrimp and lobster), and found that despite extensive sequence and structural homology across metazoans, dynamic behavior - particularly long range structural fluctuations - were clearly distinct between phyla. Vertebrate Tpms were flexible and sampled complex, multi-state conformational landscapes. Invertebrate Tpms were rigid, sampling highly constrained harmonic landscapes. Filtering of trajectories by PCA into essential subspaces showed significant overlap within but not between phyla. In vertebrate Tpms, hinge-regions decoupled long-range inter-helical motions and suggested distinct domains. In contrast, crustacean Tpms lacked significant long range dynamic correlations - behaving more like a single rigid rod. Although Tpm sequence and structure has highly conserved over the last 0.6-billion years since the split of ancestral bilateria into protostomes and deuterostomes, divergence seems to have occurred at the level of long-range correlated dynamics, reflecting adaptations to phyla-specific requirements of actin binding and muscle contraction.
- Posted April 13, 2018.
