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Side-chain Contributions to Membrane Protein Structure and Stability.

机译:侧链对膜蛋白结构和稳定性的贡献。

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摘要

The molecular forces that stabilize membrane protein structure are poorly understood. To investigate these forces we introduced alanine substitutions at 24 positions in the B helix of bacteriorhodopsin and examined their effects on structure and stability. Although most of the results can be rationalized in terms of the folded structure, there are a number of surprises. (1) We find a remarkably high frequency of stabilizing mutations (17%), indicating that membrane proteins are not highly optimized for stability. (2) Helix B is kinked, with the kink centered around Pro50. The P50A mutation has no effect on stability, however, and a crystal structure reveals that the helix remains bent, indicating that tertiary contacts dominate in the distortion of this helix. (3) We find that the protein is stabilized by about 1kcal/mol for every 38A(2) of surface area buried, which is quite similar to soluble proteins in spite of their dramatically different environments. (4) We find little energetic difference, on average, in the burial of apolar surface or polar surface area, implying that van der Waals packing is the dominant force that drives membrane protein folding.
机译:稳定膜蛋白结构的分子力了解甚少。为了研究这些力,我们在细菌视紫红质的B螺旋中的24个位置引入了丙氨酸取代,并研究了它们对结构和稳定性的影响。尽管就折叠结构而言,大多数结果都可以合理化,但仍有许多惊喜。 (1)我们发现稳定突变的频率非常高(17%),这表明膜蛋白的稳定性没有高度优化。 (2)螺旋B扭结,扭结以Pro50为中心。 P50A突变对稳定性没有影响,但是晶体结构显示该螺旋保持弯曲状态,表明三级接触在该螺旋的变形中起主要作用。 (3)我们发现,每埋入38A(2)表面积的蛋白质,其稳定度约为1kcal / mol,这与可溶性蛋白质非常相似,尽管它们的环境截然不同。 (4)平均而言,在非极性表面或极性表面区域的埋葬中,我们发现几乎没有能量差异,这表明范德华堆积是驱动膜蛋白折叠的主要力量。

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