Attwood T K, Findlay J B
Department of Biochemistry and Molecular Biology, University of Leeds, UK.
Protein Eng. 1994 Feb;7(2):195-203. doi: 10.1093/protein/7.2.195.
Recently we reported the design of a discriminating fingerprint for rhodopsin-like G-protein-coupled receptors (GPCRs). The fingerprint encodes the seven putative membrane-spanning motifs and was potently diagnostic of all GPCRs (52 in all) in version 8.1 of the OWL composite sequence database, readily distinguishing them from all other integral membrane proteins. With a 3-fold increase in the size of OWL, the fingerprint has been updated and now finds 332 receptors that match all the motifs. The situation, however, has grown in complexity: 61 sequences make imperfect matches with the fingerprint, yielding a total of 393 'hits'. The bulk of the partial hits are olfactory receptors: these appear to fall into discrete subfamilies in which one or more of the transmembrane motifs are either poorly matched or are not matched at all. These results are supported by preliminary phylogenetic analyses, which show the olfactory and various other partial matches clustering away from the main body of true hits. The approach has provided a powerful diagnostic tool for identifying GPCRs, and results are consistent with previous observations that the pheromone, cAMP and secretin-like receptors belong to separate families--these bear their own unique sequence fingerprints by which they may be distinguished from the rhodopsin-like superfamily.
最近我们报道了一种针对视紫红质样G蛋白偶联受体（GPCRs）的鉴别性指纹图谱的设计。该指纹图谱对七个假定的跨膜基序进行编码，并且在OWL复合序列数据库8.1版本中对所有GPCRs（共52种）具有强大的诊断能力，能轻易地将它们与所有其他整合膜蛋白区分开来。随着OWL规模扩大了3倍，该指纹图谱已得到更新，现在发现有332种受体与所有基序匹配。然而，情况变得更加复杂：有61个序列与指纹图谱存在不完全匹配，总共产生393个“命中结果”。大部分部分匹配结果是嗅觉受体：它们似乎分成不同的亚家族，其中一个或多个跨膜基序要么匹配不佳，要么完全不匹配。这些结果得到了初步系统发育分析的支持，该分析表明嗅觉受体和其他各种部分匹配结果与真正命中结果的主体聚类分离。该方法为识别GPCRs提供了一种强大的诊断工具，结果与之前的观察结果一致，即信息素、cAMP和促胰液素样受体属于不同的家族——它们具有各自独特的序列指纹图谱，借此可与视紫红质样超家族区分开来。
