Institut de Biotecnologia i de Biomedicina (IBB) and Dept. de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
Institut de Investigacions Biomèdiques Agustí Pi i Sunyer (IDIBABS), Barcelona 08036, Spain.
J Mol Biol. 2022 Dec 30;434(24):167875. doi: 10.1016/j.jmb.2022.167875. Epub 2022 Nov 2.
SUMO proteases or deSUMOylases regulate the lifetime of SUMO-conjugated targets in the cell by cleaving off the isopetidic bond between the substrate and the SUMO modifier, thus reversing the conjugation activity of the SUMO E3 ligases. In humans the deSUMOylating activity is mainly conducted by the SENP/ULP protease family, which is constituted of six members sharing a homologous catalytic globular domain. SENP6 and SENP7 are the most divergent members of the family and they show a unique SUMO2/3 isoform preference and a particular activity for dismantling polySUMO2 chains. Here, we present the crystal structure of the catalytic domain of human SENP7 bound to SUMO2, revealing structural key elements for the SUMO2 isoform specificity of SENP7. In particular, we describe the specific contacts between SUMO2 and a unique insertion in SENP7 (named Loop1) that is responsible for the SUMO2 isoform specificity. All the other interface contacts between SENP7 and SUMO2, including the SUMO2 C-terminal tail interaction, are conserved among members of the SENP/ULP family. Our data give insight into an evolutionary adaptation to restrict the deSUMOylating activity in SENP6 and SENP7 for the SUMO2/3 isoforms.
SUMO 蛋白酶或去 SUMO 酶通过切断基质和 SUMO 修饰物之间的异肽键，从而逆转 SUMO E3 连接酶的连接活性，来调节细胞中 SUMO 缀合靶标的寿命。在人类中，去 SUMO 化活性主要由 SENP/ULP 蛋白酶家族进行，该家族由六个具有同源催化球状结构域的成员组成。SENP6 和 SENP7 是该家族中最具差异的成员，它们表现出独特的 SUMO2/3 亚型偏好和拆卸多 SUMO2 链的特殊活性。在这里，我们展示了与人 SENP7 的催化结构域结合的 SUMO2 的晶体结构，揭示了 SENP7 对 SUMO2 亚型特异性的结构关键要素。特别是，我们描述了 SUMO2 与 SENP7 中独特插入物（命名为 Loop1）之间的特定接触，该插入物负责 SUMO2 亚型特异性。SENP7 和 SUMO2 之间的所有其他界面接触，包括 SUMO2 C 末端尾部相互作用，在 SENP/ULP 家族成员中是保守的。我们的数据深入了解了一种进化适应，以限制 SENP6 和 SENP7 对 SUMO2/3 亚型的去 SUMO 化活性。
