Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase
Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase
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DOI：
10.1126/science.1110340
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发表时间：
2005-07-01
期刊：
影响因子：
56.9
通讯作者：
Coscoy, L
中科院分区：
文献类型：
--
作者：
Cadwell, K;Coscoy, L
泛素化控制广泛的细胞功能。泛素化途径的最后一步由酶3型（E3）泛素连接酶调节。E3酶负责底物特异性并催化底物的赖氨酸残基（或底物的N末端）和泛素之间的异肽键的形成。MIR 1和MIR 2是卡波西肉瘤相关疱疹病毒编码的两种E3泛素连接酶，介导I类主要组织相容性复合体（MHC 1）分子的泛素化和随后的内化。在这里，我们发现，MIR 1，而不是MIR 2，促进下调的MHC I分子缺乏赖氨酸残基在其胞质内域。在MIR 1的存在下，这些MHC I分子被泛素化，并且它们与泛素的结合对P β（2）-巯基乙醇敏感，不像赖氨酸-泛素键。这种形式的泛素化需要在MHC I分子的胞质内尾部的半胱氨酸残基。在人工甘氨酸和atanine胞质内结构域中含有单个半胱氨酸残基的MHC I分子在MIR 1存在下被内吞和降解。因此，泛素化可以发生在缺乏可接近赖氨酸或可接近N末端的蛋白质上。
Ubiquitination controls a broad range of cellular functions. The last step of the ubiquitination pathway is regulated by enzyme type 3 (E3) ubiquitin ligases. E3 enzymes are responsible for substrate specificity and catalyze the formation of an isopeptide bond between a lysine residue of the substrate (or the N terminus of the substrate) and ubiquitin. MIR1 and MIR2 are two E3 ubiquitin ligases encoded by Kaposi's sarcoma-associated herpesvirus that mediate the ubiquitination of major histocompatibility complex class I (MHC 1) molecules and subsequent internalization. Here, we found that MIR1, but not MIR2, promoted down-regulation of MHC I molecules lacking lysine residues in their intracytoplasmic domain. In the presence of MIR1, these MHC I molecules were ubiquitinated, and their association with ubiquitin was sensitive to P beta(2)-mercaptoethanol, unlike lysine-ubiquitin bonds. This form of ubiquitination required a cysteine residue in the intracytoplasmic tail of MHC I molecules. An MHC I molecule containing a single cysteine residue in an artificial glycine and atanine intracytoplasmic domain was endocytosed and degraded in the presence of MIR1. Thus, ubiquitination can occur on proteins lacking accessible lysines or an accessible N terminus.