ON THE USE OF SEQUENCE HOMOLOGIES TO PREDICT PROTEIN-STRUCTURE - IDENTICAL PENTAPEPTIDES CAN HAVE COMPLETELY DIFFERENT CONFORMATIONS
ON THE USE OF SEQUENCE HOMOLOGIES TO PREDICT PROTEIN-STRUCTURE - IDENTICAL PENTAPEPTIDES CAN HAVE COMPLETELY DIFFERENT CONFORMATIONS
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DOI：
10.1073/pnas.81.4.1075
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发表时间：
1984-01-01
期刊：
影响因子：
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通讯作者：
SANDER, C
中科院分区：
文献类型：
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作者：
KABSCH, W;SANDER, C
氨基酸序列同源性的搜索是预测蛋白质结构的有力工具。发现的序列同源性目前用于预测癌基因蛋白质的功能。为了使这一工具更加锋利，短序列同源性的结构意义进行了研究，通过搜索已知的三维结构的蛋白质的子序列身份。在62个具有10，000个残基的蛋白质中，不相关蛋白质之间最长的分离同源性为5个残基长。 在6个（25个中的）情况中，存在令人惊讶的结构适应性：相同的5个残基是α-半胱氨酸的一部分。一种蛋白质中的螺旋和一部分β-另一种蛋白质中。这些例子定量地表明，蛋白质内的五肽结构强烈依赖于序列背景，这是大多数蛋白质结构预测方法基本上忽略的事实：仅考虑5个残基的局部序列不足以正确预测局部构象（二级结构）。必须考虑长度为6或更长的协同性。此外，在将新蛋白质序列与已知序列的数据库进行比较的日益增长的实践中，在2种蛋白质之间发现相同的五肽序列并不是结构相似性或进化亲缘关系的重要指示。
The search for amino acid sequence homologies can be a powerful tool for predicting protein structure. Discovered sequence homologies are currently used in predicting the function of oncogene proteins. To sharpen this tool, the structural significance of short sequence homologies was investigated by searching proteins of known 3-dimensional structure for subsequence identities. In 62 proteins with 10,000 residues, the longest isolated homologies between unrelated proteins are 5 residues long. In 6 (out of 25) cases there was surprising structural adaptability: the same 5 residues are part of an .alpha.-helix in one protein and part of a .beta.-strand in another protein. These examples show quantitatively that pentapeptide structure within a protein is strongly dependent on sequence context, a fact essentially ignored in most protein structure prediction methods: just considering the local sequence of 5 residues is not sufficient to predict correctly the local conformation (secondary structure). Cooperativity of length 6 or longer must be taken into account. Also, in the growing practice of comparing a new protein sequence with a data base of known sequences, finding an identical pentapeptide sequence between 2 proteins is not a significant indication of structural similarity or of evolutionary kinship.