Perutz M F, Johnson T, Suzuki M, Finch J T
Medical Research Council Laboratory of Molecular Biology, Cambridge, England.
Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5355-8. doi: 10.1073/pnas.91.12.5355.
Four inherited neurodegenerative diseases are linked to abnormally expanded repeats of glutamine residues in the affected proteins. Molecular modeling followed by optical, electron, and x-ray diffraction studies of a synthetic poly(L-glutamine) shows that it forms beta-sheets strongly held together by hydrogen bonds. Glutamine repeats may function as polar zippers, for example, by joining specific transcription factors bound to separate DNA segments. Their extension may cause disease either by increased, nonspecific affinity between such factors or by gradual precipitation of the affected proteins in neurons.
四种遗传性神经退行性疾病与受影响蛋白质中谷氨酰胺残基异常扩展的重复序列有关。对合成的聚（L-谷氨酰胺）进行分子建模，随后进行光学、电子和X射线衍射研究，结果表明它形成了通过氢键紧密结合在一起的β-折叠。谷氨酰胺重复序列可能起到极性拉链的作用，例如，通过连接与分开的DNA片段结合的特定转录因子。它们的延伸可能通过这些因子之间增加的非特异性亲和力或通过受影响蛋白质在神经元中的逐渐沉淀而导致疾病。
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