第12讲蛋白质功能分析与预测.ppt

* * * The top sequence in all three triplets of proteins is the fused domain or Rosetta Stone sequence; it is homologous to two separate sequences in another species. In the middle example, the genes Pur2 and Pur3 of yeast both encode enzymes that catalyse steps in the purine biosynthetic pathway. If it were not previously known from biochemical and genetic experiments that these enzymes are functionally linked, the linkage would be apparent from the Rosetta stone sequence Ade5,7,8 from Caenorhabditis elegans. Similarly, in the lower example, the fused sequence of TrpC in the Escherichia coli genome would inform us that the yeast proteins TrG and TrpF are functionally linked, if we did not know already that they both catalyse steps in the biosynthesis of tryptophan. * 在原核生物中，即使经过了很长的进化距离，一些基因簇在其相对位置上表现出了很好的保守性。进一步研究发现，这些基因常常具有功能的相互作用，并且往往是同一个操纵元的组成部分。Overbeek等和Dandekar等提出可以利用这一信息预测功能。在一些真核生物中，一些共调控的基因也出现上述现象，但是真核生物中这种信号很弱，没有被用于功能预测。 * The best starting searches are FASTA, BLAST, and PSI-BLAST, which provide accurate and fast database searching for known similar sequences. If this search does not produce satisfactory results, one may perform several related queries to sequence and structure motif prediction servers (if the structure is not available) or analyses based on high-throughput experimental results (if the experimental data is available). Web resources for structure-based function prediction FATCAT: Flexible structure AlignmenT by Chaining AFPs (Aligned Fragment Pairs) allowing Twists / RaptorX: a Web Portal for Protein Structure and Function Prediction 使用蛋白质相互作用数据预测功能近几年成为新的研究热点。 这些研究一般都基于这样的假设:即两个蛋白质它们的相互作用蛋白质重合越多在功能上就越可能相关。 3.5基于相互作用的蛋白质功能预测 The evolution of the meaning of protein function. The traditional view is illustrated on the left, and the post-genomic view on the right. 蛋白质A 蛋白质B 转录活性 转录活性 蛋白质之间相互作用以及通过相互作用而形成的蛋白复合物是细胞各种基本功能的主要完成者。 蛋白质A具有转录功能，蛋白质B可以与蛋白质A相互作用，因而蛋白质B可能与基因转录相关 Transcription initiation complex Translation initiation complex 基于相互作