Haas A L, Siepmann T J
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226, USA.
FASEB J. 1997 Dec;11(14):1257-68. doi: 10.1096/fasebj.11.14.9409544.
The covalent attachment of the polypeptide ubiquitin to proteins marks them for degradation by the ubiquitin/26S proteasome-dependent degradation pathway. This pathway functions in regulating many fundamental processes required for cell viability. Phylogenetic analysis of ubiquitin sequences reveals greater variability among lower eukaryotes and defines essential residues, many of which are conserved among the three ubiquitin-like proteins known to undergo parallel ligation pathways. The hierarchical design of the ubiquitin conjugation mechanism provides great flexibility for the divergent evolution of new functions mediated by this posttranslational modification. Within this hierarchy, a single ubiquitin-activating enzyme provides charged intermediates to multiple targeting pathways defined by cognate ubiquitin carrier protein (E2)/ligase (E3) pairs. Sequence analysis of E2 isozymes shows that the E2 superfamily is composed of distinct function-specific families. The apparent lack of E2/E3 specificity suggested in the literature results from the presence of multiple isozymes within many E2 families and erroneous family assignments based on incomplete data sets. Other apparent inconsistencies are explained by interfamily sequence relationships among some E2 isoforms.
多肽泛素与蛋白质的共价连接标志着它们将通过泛素/26S蛋白酶体依赖性降解途径被降解。该途径在调节细胞生存所需的许多基本过程中发挥作用。泛素序列的系统发育分析揭示了低等真核生物之间更大的变异性，并确定了必需残基，其中许多残基在已知经历平行连接途径的三种泛素样蛋白中是保守的。泛素缀合机制的分层设计为这种翻译后修饰介导的新功能的分歧进化提供了极大的灵活性。在这个层次结构中，单个泛素激活酶为同源泛素载体蛋白（E2）/连接酶（E3）对定义的多个靶向途径提供带电中间体。E2同工酶的序列分析表明，E2超家族由不同的功能特异性家族组成。文献中提出的明显缺乏E2/E3特异性是由于许多E2家族中存在多种同工酶以及基于不完整数据集的错误家族分配。其他明显的不一致性可以通过一些E2同工型之间的家族间序列关系来解释。
