OPTIMAL PROTEIN-STRUCTURE ALIGNMENTS BY MULTIPLE LINKAGE CLUSTERING - APPLICATION TO DISTANTLY RELATED PROTEINS
OPTIMAL PROTEIN-STRUCTURE ALIGNMENTS BY MULTIPLE LINKAGE CLUSTERING - APPLICATION TO DISTANTLY RELATED PROTEINS
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DOI：
10.1093/protein/8.7.647
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发表时间：
1995-07-01
期刊：
影响因子：
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通讯作者：
WODAK, SJ
中科院分区：
文献类型：
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作者：
BOUTONNET, NS;ROOMAN, MJ;WODAK, SJ
本文提出了一种全自动的蛋白质结构比对方法。重叠的骨架原子（N、C-alpha、C-C和O）的偏差，并被设计为产生关于该测量的最优解。在第一步中，该程序鉴定两种蛋白质中具有相似构象的蛋白质片段。在第二步中，使用一种新的多连锁聚类算法来识别产生最佳全局结构比对的片段组合。对于给定的蛋白质对，通常可以获得几个结构比对，这里利用它们来自动定义蛋白质家族的共同结构核心。此外，描述了聚类树的自动分析，其能够检测结构元件之间的刚体运动。为了说明我们的过程的性能，我们将其应用于远亲蛋白质家族，一组为三种α + β蛋白质泛素、铁氧还蛋白和蛋白质G的B1结构域。它们的共同结构基序由四条β-链和唯一的α-螺旋组成，其中一条链和螺旋相对于其余三条β-链作为刚体移位。另一个家族由来自希腊关键组的β-蛋白组成，特别是放线菌黄质、免疫球蛋白可变结构域和质体蓝素，它们的共有基序由五条β-链和一个转角组成，在除胰蛋白酶之外的所有希腊关键蛋白中被鉴定为基本完整，并且有趣的是在另外三个β-蛋白家族中，脂质运载蛋白、神经氨酸酶和凝集素，这一结果提供了新的见解的进化关系在非常不同的组的所有β蛋白质。
A fully automatic procedure for aligning two protein structures is presented, It uses as sole structural similarity measure the root mean square (r.m.s.) deviation of superimposed backbone atoms (N, C-alpha,C- C and O) and is designed to yield optimal solutions with respect to this measure, In a first step, the procedure identifies protein segments with similar conformations in both proteins. In a second step, a novel multiple linkage clustering algorithm is used to identify segment combinations which yield optimal global structure alignments, Several structure alignments can usually be obtained for a given pair of proteins, which are exploited here to define automatically the common structural core of a protein family, Furthermore, an automatic analysis of the clustering trees is described which enables detection of rigid-body movements between structure elements, To illustrate the performance of our procedure, we apply it to families of distantly related proteins, One groups the three alpha+beta proteins ubiquitin, ferredoxin and the B1-domain of protein G. Their common structure motif consists of four beta-strands and the only a-helix, with one strand and the helix being displaced as a rigid body relative to the remaining three beta-strands. The other family consists of beta-proteins from the Greek key group, in particular actinoxanthin, the immunoglobulin variable domain and plastocyanin, Their consensus motif, composed of five beta-strands and a turn, is identified, mostly intact, in all Greek key proteins except the trypsins, and interestingly also in three other beta-protein families, the lipocalins, the neuraminidases and the lectins, This result provides new insights into the evolutionary relationships in the very diverse group of all beta-proteins.