Kim Man Su, Kim Jeom-A, Song Hyun Kyu, Jeon Hyesung
Biomedical Research Center, Korea Institute of Science and Technology, Seongbuk-gu, Seoul 136-791, South Korea.
Biochem Biophys Res Commun. 2006 Dec 22;351(3):612-8. doi: 10.1016/j.bbrc.2006.10.068. Epub 2006 Oct 20.
Signal transducing adaptor molecule (STAM) complexed with hepatocyte growth factor regulated tyrosine kinase substrate (Hrs) works on sorting of cargo proteins in multivesicular body (MVB) pathway. Associated molecule with SH3 domain of STAM (AMSH), a zinc-containing ubiquitin isopeptidase, is thought to play a role in regulation of ubiquitin-mediated degradation by binding to STAM. We have found that AMSH requires the conformation of Px(V/I)(D/N)RxxKP sequence to bind SH3 domain of STAM with approximately 7 microM affinity, and that the isolated C-terminal domain of AMSH contains the isopeptidase activity. Deubiquitination by AMSH was assisted when ubiquitins were bound to STAM which can bind to AMSH simultaneously. With the specificity toward K63-linked ubiquitins, this facilitated ubiquitin processing activity of AMSH may imply a distinct regulatory mechanism for sorting and degradation through STAM binding.
与肝细胞生长因子调节的酪氨酸激酶底物（Hrs）复合的信号转导衔接分子（STAM）在多泡体（MVB）途径中参与货物蛋白的分选。含SH3结构域的STAM相关分子（AMSH）是一种含锌的泛素异肽酶，被认为通过与STAM结合在泛素介导的降解调节中发挥作用。我们发现，AMSH需要Px(V/I)(D/N)RxxKP序列的构象以约7微摩尔的亲和力结合STAM的SH3结构域，并且AMSH的分离的C末端结构域具有异肽酶活性。当泛素与可同时结合AMSH的STAM结合时，AMSH的去泛素化作用得到促进。由于对K63连接的泛素有特异性，AMSH这种促进的泛素加工活性可能意味着通过STAM结合进行分选和降解的独特调节机制。
