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A critical residue in the folding pathway of an integral membrane protein.

机译:完整膜蛋白折叠途径中的关键残基。

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摘要

Although a number of common diseases are a direct consequence of membrane protein misfolding, studies of membrane protein folding and misfolding lag well behind those of soluble proteins. Here it is shown that an interfacial residue, Tyr16, of the integral membrane protein diacylglycerol kinase (DAGK) plays a critical role in the folding pathway of this protein. Properly folded Y16C exhibits kinetic parameters and stability similar to wild-type DAGK. However, when unfolded and then allowed to spontaneously fold in the presence of model membranes, Y16C exhibits dramatically lower rates and efficiencies of functional assembly compared to the wild-type protein. The Y16C mutant represents a class of mutations which may be commonly found in disease-related membrane proteins.
机译:尽管许多常见疾病是膜蛋白错误折叠的直接结果,但对膜蛋白折叠和错误折叠的研究却远远落后于可溶性蛋白。此处显示完整膜蛋白二酰基甘油激酶(DAGK)的界面残基Tyr16在该蛋白的折叠途径中起关键作用。正确折叠的Y16C具有类似于野生型DAGK的动力学参数和稳定性。但是,当展开并随后在模型膜存在下自发折叠时,与野生型蛋白相比,Y16C的功能组装效率和效率大大降低。 Y16C突变体代表一类可能在疾病相关膜蛋白中常见的突变。

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