MODELING OF THE 3-DIMENSIONAL STRUCTURE OF PROTEINS WITH THE TYPICAL LEUCINE-RICH REPEATS
MODELING OF THE 3-DIMENSIONAL STRUCTURE OF PROTEINS WITH THE TYPICAL LEUCINE-RICH REPEATS
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DOI：
10.1016/s0969-2126(01)00222-2
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发表时间：
1995-09-15
期刊：
影响因子：
5.7
通讯作者：
WODAK, SJ
中科院分区：
文献类型：
--
作者：
KAJAVA, AV;VASSART, G;WODAK, SJ
背景：富含亮氨酸重复序列（LRR）存在于具有多种功能的蛋白质中。核糖核酸酶抑制剂 (RI) 的马蹄形结构，在马蹄内圆周上排列有平行的 β 片层，和/或在其外圆周两侧有螺旋，是唯一包含这些待确定重复序列的 X 射线结构。尽管 RI 重复序列的长度和序列与最常见的 LRR 不同，但使用 RI 结构作为模板，得出这些更典型的 LRR 蛋白的三维结构框架被认为是值得的。 结果：通过谱搜索获得了来自 68 个蛋白的 569 个 LRR 的序列比对，并用于比较序列分析，以区分具有可能的结构作用的残基和似乎对功能至关重要的残基。这些知识与已知的 RI 原子结构一起用于对最常见的 LRR 单元的三维结构进行建模。然后使用这些模型单元构建促甲状腺素受体 (TSHR)（一种“典型”LRR 蛋白）胞外结构域的三维结构。结论：模型化的 TSHR 结构采用非球状排列，与 RI 中的结构类似。这种典型LRR蛋白的β区域与RI结构相同，而α螺旋较短，并且αβ和βα连接的构象不同。由于这些差异，不可能使用重复（如 RI 中发现的重复）将典型的 LRR 单元包装在一起。这种互斥关系得到了序列分析的支持。此处获得的典型 LRR 的预测结构可用于为任何已知的 LRR 蛋白质构建模型，并且用于预测的方法可应用于包含内部重复的其他蛋白质。
Background: Leucine-rich repeats (LRRs) are present in proteins with diverse functions. The horseshoe-shaped structure of a ribonuclease inhibitor (RI), with a parallel beta sheet lining the inner circumference of the horseshoe and or helices flanking its outer circumference, is the only X-ray structure containing these repeats to be determined. Despite the fact that the lengths and sequences of the RI repeats differ from those of the most commonly occurring LRRs, it was deemed worthwhile to derive a three-dimensional structural framework of these more typical LRR proteins, using the RI structure as a template.Results: Sequence alignments of 569 LRRs from 68 proteins were obtained by a profile search and used in a comparative sequence analysis to distinguish between residues with a probable structural role and those which seemed essential for function. This knowledge, along with the known atomic structure of RI, was used to model the three-dimensional structure of the most common LRR units. These modeled units were then used to build the three-dimensional structure of the extracellular domain of the thyrotropin receptor (TSHR) - a 'typical' LRR protein.Conclusions: The modeled TSHR structure adopts a non-globular arrangement, similar to that in RI. The beta regions of this typical LRR protein are the same as in the RI structure, whereas the a helices are shorter and the conformations of the alpha beta and beta alpha connections are different. As a result of these differences it was not possible to pack together typical LRR units using repeats such as those found in RI. This mutually exclusive relationship is supported by sequence analysis. The predicted structure of the typical LRRs obtained here can be used to build models for any of the known LRR proteins and the approach used for the prediction could be applied to other proteins containing internal repeats.