'Something in the way she moves': The functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI).
'Something in the way she moves': The functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI).
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DOI：
10.1016/j.bbapap.2017.08.014
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Römer RA
中科院分区：
文献类型：
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作者：
Freedman RB;Desmond JL;Byrne LJ;Heal JW;Howard MJ;Sanghera N;Walker KL;Wallis AK;Wells SA;Williamson RA;Römer RA
蛋白质二硫键异构酶（PDI）在内质网中具有多种功能，如氧化还原转移、二硫键异构化和氧化蛋白质折叠的催化剂、分子伴侣和多亚基复合体。它与非常广泛的底物和伴侣蛋白相互作用，但这些相互作用的结构信息有限。关于PDI在溶液中的灵活性的广泛证据与其运动范围的任何详细图片都不匹配。一种新的快速方法来模拟大蛋白的运动提供详细的分子轨迹的PDI展示了广泛的变化，其四个结构域的相对方向，关键位点之间的距离和内部运动的核心配体结合域的变化很大。审查表明，这些模拟与实验证据是一致的，并提供深入了解广泛的灵活运动的PDI所赋予的功能能力。
Protein disulfide isomerase (PDI) has diverse functions in the endoplasmic reticulum as catalyst of redox transfer, disulfide isomerization and oxidative protein folding, as molecular chaperone and in multi-subunit complexes. It interacts with an extraordinarily wide range of substrate and partner proteins, but there is only limited structural information on these interactions. Extensive evidence on the flexibility of PDI in solution is not matched by any detailed picture of the scope of its motion. A new rapid method for simulating the motion of large proteins provides detailed molecular trajectories for PDI demonstrating extensive changes in the relative orientation of its four domains, great variation in the distances between key sites and internal motion within the core ligand-binding domain. The review shows that these simulations are consistent with experimental evidence and provide insight into the functional capabilities conferred by the extensive flexible motion of PDI.