Danot Olivier, Marquenet Emélie, Vidal-Ingigliardi Dominique, Richet Evelyne
Institut Pasteur, Molecular Genetics Unit and CNRS URA2172, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Structure. 2009 Feb 13;17(2):172-82. doi: 10.1016/j.str.2009.01.001.
The signal transduction ATPases with numerous domains (STAND) represent a newly recognized class of widespread, sophisticated ATPases that are related to the AAA+ proteins and that function as signaling hubs. These proteins control diverse biological processes in bacteria and eukaryotes, including gene expression, apoptosis, and innate immunity responses. They function as tightly regulated switches, with the off and on positions corresponding to a long-lived monomeric, ADP-bound form and a multimeric, ATP-bound form, respectively. Inducer binding to the sensor domain activates the protein by promoting ADP for ATP exchange, probably through removal of an intramolecular inhibitory interaction, whereas ATP hydrolysis turns off the protein. One key component of the switch is a three-domain module carrying the ATPase activity (nucleotide-binding oligomerization domain [NOD]). Analysis of the atomic structures of four crystallized nucleotide-bound NOD modules provides an unprecedented insight into the NOD conformational changes underlying the activation process.
具有多个结构域的信号转导ATP酶（STAND）代表了一类新认识的广泛存在且复杂的ATP酶，它们与AAA +蛋白相关，并作为信号枢纽发挥作用。这些蛋白质控制细菌和真核生物中的多种生物学过程，包括基因表达、细胞凋亡和先天免疫反应。它们作为严格调控的开关发挥作用，关闭和开启位置分别对应于长寿的单体ADP结合形式和多聚体ATP结合形式。诱导剂与传感器结构域结合通过促进ADP与ATP交换来激活蛋白质，这可能是通过消除分子内抑制性相互作用实现的，而ATP水解则使蛋白质失活。开关的一个关键组件是携带ATP酶活性的三结构域模块（核苷酸结合寡聚化结构域[NOD]）。对四个结晶的核苷酸结合NOD模块的原子结构分析为激活过程背后的NOD构象变化提供了前所未有的见解。
