人膜相关蛋白TEB4的结构及其E3连接酶活性

Structure of Human Membrane-Associated Protein TEB4 and Its E3 Ligase Activity

TEB4(MARCH Ⅳ)是酵母Doa10的同源体,作为E3连接酶参与内质网相关蛋白的降解。TEB4和酵母Doa10定位于内质网上,包含一个环指域和多个跨膜域。这个环指结构位于蛋白的N端,具有特殊的C4HC3结构。在泛素结合酶UBC7参与的底物第48位赖氨酸特异点的泛素化反应中,分离开的环指域在细胞液中催化泛素的连接。这些特性与E3酶有关,E3酶是参与内质网相关蛋白降解的重要酶。和一些E3连接酶一样,TEB4可能参与神经退行性病变的调节。

TEB4 （MARCH VI） is the homolog of yeast Doa10, an E3 ligase involved in ERassociated degradation. TEB4 and Doa10 are ER-resident, containing a conserved RING finger and large predicted transmembrane domains. They have an unconventional RING-CH domain near its Nterminus. The isolated RING domain catalyses ubiquitin ligation in vitro in a reaction that is ubiquitin Lys48-speeifie and involves UBC7 （ubiquitin-eonjugating enzyme 7）. These properties are related to E3 enzymes, which are involved in ER-assoeiated protein degradation. Like some E3 ligases, TEB4 may play a role in the regulation of the neurodegenerative disorders.