Fung Angela Wai S, Fahlman Richard P
474 Medical Sciences Building, Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.
Curr Protein Pept Sci. 2015;16(2):163-80.
The N-end rule pathway is a conserved targeted proteolytic process observed in organisms ranging from eubacteria to mammals. The N-end rule relates the metabolic stability of a protein to its N-terminal amino acid residue. The identity of the N-terminal amino acid residue is a primary degradation signal, often referred to as an N-degron, which is recognized by the components of the N-end rule when it is a destabilizing N-terminus. N-degrons may be exposed by non-processive proteolytic cleavages or by post-translational modifications. One modification is the post-translational addition of amino acids to the N-termini of proteins, a reaction catalyzed by aminoacyl-tRNA protein transferases. The aminoacyl-tRNA protein transferase in eubacteria like Escherichia coli is L/F transferase. Recent investigations have reported unexpected observations regarding the L/F transferase catalytic mechanism and its mechanisms of substrate recognition. Additionally, recent proteome-wide identification of putative in vivo substrates facilitates hypothesis into the yet elusive biological functions of the prokaryotic N-end rule pathway. Here we summarize the recent findings on the molecular mechanisms of catalysis and substrate recognition by the E. coli L/F transferase in the prokaryotic N-end rule pathway.
N端规则途径是一种保守的靶向蛋白水解过程，在从真细菌到哺乳动物的各种生物体中都能观察到。N端规则将蛋白质的代谢稳定性与其N端氨基酸残基联系起来。N端氨基酸残基的身份是一个主要的降解信号，通常被称为N-degron，当它是一个不稳定的N端时，会被N端规则的组分识别。N-degrons可能通过非持续性蛋白水解切割或翻译后修饰而暴露。一种修饰是在蛋白质的N端进行氨基酸的翻译后添加，这是一种由氨酰-tRNA蛋白质转移酶催化的反应。像大肠杆菌这样的真细菌中的氨酰-tRNA蛋白质转移酶是L/F转移酶。最近的研究报告了关于L/F转移酶催化机制及其底物识别机制的意外发现。此外，最近在全蛋白质组范围内对假定的体内底物的鉴定有助于对原核生物N端规则途径尚未明确的生物学功能提出假设。在这里，我们总结了关于原核生物N端规则途径中大肠杆菌L/F转移酶的催化和底物识别分子机制的最新发现。
