Structure of the mid-region of tropomyosin: Bending and binding sites for actin
Structure of the mid-region of tropomyosin: Bending and binding sites for actin
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DOI：
10.1073/pnas.0509269102
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发表时间：
2005-12-27
影响因子：
11.1
通讯作者：
Cohen, C
中科院分区：
文献类型：
--
作者：
Brown, JH;Zhou, ZC;Cohen, C
原肌球蛋白是一种双链α-螺旋卷曲螺旋，其与F-肌动蛋白螺旋的周期性相互作用对于细丝的稳定和肌肉收缩的调节至关重要。在这里，我们推断这些相互作用的机械和化学基础，从2.3埃分辨率的晶体结构的中间三个原肌球蛋白的七个时期。卷曲螺旋的几何特定弯曲（由核心丙氨酸簇产生）和围绕核心间隙的可变弯曲（由孤立丙氨酸产生）沿分子沿着发生。晶体包装是值得注意的，这意味着功能上重要的第五期包括一个特别有利的蛋白质结合位点，包括一个不寻常的非极性补丁的表面上连同周围的带电残基。基于这些和其他结果，我们构建了一个特定的细灯丝模型，每个周期的N端半部（即，所谓的“α区”）与F-肌动蛋白中每个单体的亚结构域3轴向对齐。
Tropomyosin is a two-chain a-helical coiled coil whose periodic interactions with the F-actin helix are critical for thin filament stabilization and the regulation of muscle contraction. Here we deduce the mechanical and chemical basis of these interactions from the 2.3-angstrom-resolution crystal structure of the middle three of tropomyosin's seven periods. Geometrically specific bends of the coiled coil, produced by clusters of core alanines, and variable bends about gaps in the core, produced by isolated alanines, occur along the molecule. The crystal packing is notable in signifying that the functionally important fifth period includes an especially favorable protein-binding site, comprising an unusual apolar patch on the surface together with surrounding charged residues. Based on these and other results, we have constructed a specific model of the thin filament, with the N-terminal halves of each period (i.e., the so-called "alpha zones") of tropomyosin axially aligned with subdomain 3 of each monomer in F-actin.