Proline affects oligomerization of a coiled coil by inducing a kink in a long helix
Proline affects oligomerization of a coiled coil by inducing a kink in a long helix
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DOI：
10.1006/jsbi.1999.4182
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发表时间：
1999-12-30
影响因子：
3
通讯作者：
Lin, KL
中科院分区：
文献类型：
--
作者：
Chang, DK;Cheng, SF;Lin, KL
用核磁共振和圆二色性（CD）光谱研究了三氟乙醇（TFE）/水介质中脯氨酸对29-mer肽及其脯氨酸类似物的结构影响，该肽衍生自HIV-1跨膜糖蛋白gp 41的亮氨酸拉链（LZ）样基序。较低的螺旋含量被发现为脯氨酸突变体的CD研究。NMR数据表明，脯氨酸的螺旋变形是局部的，主要发生在取代位点的N-末端侧。分子动力学计算显示出30度+/-10度的螺旋轴弯曲，与X射线衍射结果一致。光散射实验表明，脯氨酸取代的突变体的平均聚集数是大大低于野生型肽。从野生型和脯氨酸突变体肽的解离常数的比率，三聚体形成的自由能的差异计算为2.1千卡/摩尔，热稳定性，螺旋度，和螺旋低聚物的平均聚集数被发现是相关的。结构改变和卷曲螺旋稳定性降低可能是导致gp 41的脯氨酸突变体的生物学功能和脯氨酸取代肽的抑制作用缺陷的原因。这些效应在阐明脯氨酸在跨膜蛋白中所起的作用方面也可能是重要的。(C)北京：科学出版社.
The structural effect of a proline in a helix in trifluoroethanol (TFE)/water medium was examined on a 29-mer peptide and its proline analog derived from the leucine zipper (LZ)-like motif of gp41 (the transmembrane glycoprotein of HIV-1) by NMR and circular dichroism (CD) spectroscopies. Lower helical content was found for the proline mutant from the CD study. NMR data show that distortion of the helix by proline is local and occurs mainly on the N-terminal side of the substitution site. Molecular dynamics computation exhibits a bending of the helical axis of 30 degrees +/- 10 degrees, in agreement with X-ray diffraction results. Light-scattering experiments indicated that the average aggregation number of the proline-substituted mutant is substantially lower than that of the wild-type peptide. From the ratio of dissociation constants of the wild-type and the proline mutant peptides, the difference in free energy of trimeric formation is calculated to be 2.1 kcal/mol, Thermal stability, helicity, and the average aggregation number for the helix oligomers were found to be correlated. The structural alteration and the reduced coiled coil stability may account for the deficiency in the biological functions of the proline mutants of gp41 and in the inhibitory action of proline-substituted peptides, These effects may also be important in unraveling the roles played by proline in transmembrane proteins. (C) 1999 Academic Press.