Navon Sharon Penias, Kornberg Guy, Chen Jin, Schwartzman Tali, Tsai Albert, Puglisi Elisabetta Viani, Puglisi Joseph D, Adir Noam
Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel;
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126.
Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7166-70. doi: 10.1073/pnas.1606518113. Epub 2016 Jun 15.
Bioinformatic analysis of Escherichia coli proteomes revealed that all possible amino acid triplet sequences occur at their expected frequencies, with four exceptions. Two of the four underrepresented sequences (URSs) were shown to interfere with translation in vivo and in vitro. Enlarging the URS by a single amino acid resulted in increased translational inhibition. Single-molecule methods revealed stalling of translation at the entrance of the peptide exit tunnel of the ribosome, adjacent to ribosomal nucleotides A2062 and U2585. Interaction with these same ribosomal residues is involved in regulation of translation by longer, naturally occurring protein sequences. The E. coli exit tunnel has evidently evolved to minimize interaction with the exit tunnel and maximize the sequence diversity of the proteome, although allowing some interactions for regulatory purposes. Bioinformatic analysis of the human proteome revealed no underrepresented triplet sequences, possibly reflecting an absence of regulation by interaction with the exit tunnel.
对大肠杆菌蛋白质组的生物信息学分析表明，所有可能的氨基酸三联体序列都以预期频率出现，但有四个例外。四个低丰度序列（URS）中的两个已被证明在体内和体外都会干扰翻译。将URS增加一个氨基酸会导致翻译抑制增强。单分子方法揭示了翻译在核糖体肽出口通道入口处停滞，该位置与核糖体核苷酸A2062和U2585相邻。较长的天然存在的蛋白质序列与这些相同的核糖体残基相互作用参与翻译调控。大肠杆菌的出口通道显然已经进化，以尽量减少与出口通道的相互作用，并使蛋白质组的序列多样性最大化，尽管为了调控目的允许一些相互作用。对人类蛋白质组的生物信息学分析未发现低丰度三联体序列，这可能反映出不存在通过与出口通道相互作用进行的调控。
