Center for Advanced Biotechnology and Medicine, and the Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey.
Proteins. 2020 Feb;88(2):265-273. doi: 10.1002/prot.25797. Epub 2019 Aug 28.
Tropomyosin (Tpm) is an extended α-helical coiled-coil homodimer that regulates actinomyosin interactions in muscle. Molecular simulations of four Tpms, two from the vertebrate class Mammalia (rat and pig), and two from the invertebrate class Malacostraca (shrimp and lobster), showed that despite extensive sequence and structural homology across metazoans, dynamic behavior-particularly long-range structural fluctuations-were clearly distinct. Vertebrate Tpms were more flexible and sampled complex, multi-state conformational landscapes. Invertebrate Tpms were more rigid, sampling a highly constrained harmonic landscape. Filtering of trajectories by principle component analysis into essential subspaces showed significant overlap within but not between phyla. In vertebrate Tpms, hinge-regions decoupled long-range interhelical motions and suggested distinct domains. In contrast, crustacean Tpms did not exhibit long-range dynamic correlations-behaving more like a single rigid rod on the nanosecond time scale. These observations suggest there may be divergent mechanisms for Tpm binding to actin filaments, where conformational flexibility in mammalian Tpm allows a preorganized shape complementary to the filament surface, and where rigidity in the crustacean Tpm requires concerted bending and binding.
原肌球蛋白（Tropomyosin，Tpm）是一种伸展的α螺旋卷曲螺旋同型二聚体，可调节肌肉中的肌动球蛋白相互作用。对来自脊椎动物类群 Mammalia（大鼠和猪）的两个 Tpm 和来自无脊椎动物类群 Malacostraca（虾和龙虾）的两个 Tpm 的四个 Tpm 的分子模拟表明，尽管在整个后生动物中存在广泛的序列和结构同源性，但动态行为-特别是远程结构波动-显然是不同的。脊椎动物 Tpms 更具柔韧性，可采样复杂的多态构象景观。无脊椎动物 Tpms 更刚性，采样高度受限的谐和景观。通过主成分分析将轨迹过滤到基本子空间中，表明在门内有明显的重叠，但在门之间没有重叠。在脊椎动物 Tpms 中，铰链区域解耦了远程螺旋间运动，并提示了不同的结构域。相比之下，甲壳类 Tpms 没有表现出远程动态相关性-在纳秒时间尺度上的行为更像单个刚性棒。这些观察结果表明，Tpm 与肌动蛋白丝结合可能存在不同的机制，哺乳动物 Tpm 的构象灵活性允许与丝表面互补的预组织形状，而甲壳类 Tpm 的刚性需要协同弯曲和结合。
