Singh K, Zewge D, Groth-Vasselli B, Farnsworth P N
Department of Ophthalmology, UMDNJ-New Jersey Medical School, Newark 07103, USA.
Int J Biol Macromol. 1996 Dec;19(4):227-33. doi: 10.1016/s0141-8130(96)01131-2.
The 3D structures of alpha-crystallin, a major eye lens protein, and related small heat shock proteins are unresolved. It has been assumed that alpha-crystallin is primarily a beta-sheet globular protein similar to alpha-crystallin (Siezen and Argos, Biochim. Biophys. Acta, 1983, 748, 56-67) containing sequence repeats in its two domains (Wistow, FEBS Lett. 1985, 181, 1-6). Positional flexibility of amino acid residues and far UV-circular dichroism spectroscopy were used to investigate structural relationships among these proteins. The utility of flexibility plots for predicting protein structure is demonstrated by the excellent correlation of these plots with the known 3D X-ray structures of beta/gamma-crystallins. Similar analyses of alpha-crystallin subunits, alpha A and alpha B, and human heat shock protein 27 show that the C-terminal domains and connecting segments of these proteins are very similar while the N-terminal domains have significant structural differences. Unlike beta/gamma-crystallins, both Hsp27 and alpha-crystallin subunits are asymmetrical with highly flexible C-terminal domains. Flexibility is considered essential for protein functional activity. Therefore, the C-terminal region may play an active role in alpha-crystallin and small heat shock protein function. Differences in flexibility profiles and estimated secondary structure distribution in alpha-crystallin by three recent/updated algorithms from far UV-CD spectra support our predicted 3D structure and the concept that alpha-crystallin and members of beta/gamma superfamily are structurally dissimilar.
α-晶状体蛋白（一种主要的眼晶状体蛋白）及相关的小热休克蛋白的三维结构尚未明确。人们一直认为，α-晶状体蛋白主要是一种β-折叠球状蛋白，类似于α-晶状体蛋白（Siezen和Argos，《生物化学与生物物理学报》，1983年，748卷，56 - 67页），其两个结构域中含有序列重复（Wistow，《欧洲生物化学学会联合会快报》，1985年，181卷，1 - 6页）。利用氨基酸残基的位置灵活性和远紫外圆二色光谱来研究这些蛋白质之间的结构关系。这些图谱与β/γ-晶状体蛋白已知的三维X射线结构具有良好的相关性，证明了灵活性图谱在预测蛋白质结构方面的实用性。对α-晶状体蛋白亚基αA和αB以及人热休克蛋白27的类似分析表明，这些蛋白质的C端结构域和连接片段非常相似，而N端结构域存在显著的结构差异。与β/γ-晶状体蛋白不同，Hsp27和α-晶状体蛋白亚基都是不对称的，C端结构域具有高度灵活性。灵活性被认为是蛋白质功能活性所必需的。因此，C端区域可能在α-晶状体蛋白和小热休克蛋白的功能中发挥积极作用。通过三种最新/更新的算法从远紫外圆二色光谱估计的α-晶状体蛋白灵活性图谱和二级结构分布的差异，支持了我们预测的三维结构以及α-晶状体蛋白与β/γ超家族成员在结构上不同的概念。
