Buchberger Alexander, Schindelin Hermann, Hänzelmann Petra
Department of Biochemistry, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
FEBS Lett. 2015 Sep 14;589(19 Pt A):2578-89. doi: 10.1016/j.febslet.2015.08.028. Epub 2015 Aug 29.
p97 (also known as Cdc48, Ter94, and VCP) is an essential, abundant and highly conserved ATPase driving the turnover of ubiquitylated proteins in eukaryotes. Even though p97 is involved in highly diverse cellular pathways and processes, it exhibits hardly any substrate specificity on its own. Instead, it relies on a large number of regulatory cofactors controlling substrate specificity and turnover. The complexity as well as temporal and spatial regulation of the interactions between p97 and its cofactors is only beginning to be understood at the molecular level. Here, we give an overview on the structural framework of p97 interactions with its cofactors, the emerging principles underlying the assembly of complexes with different cofactors, and the pathogenic effects of disease-associated p97 mutations on cofactor binding.
p97（也称为Cdc48、Ter94和VCP）是一种必需的、丰富且高度保守的ATP酶，驱动真核生物中泛素化蛋白的周转。尽管p97参与了高度多样的细胞途径和过程，但它自身几乎不表现出任何底物特异性。相反，它依赖于大量控制底物特异性和周转的调节辅因子。p97与其辅因子之间相互作用的复杂性以及时间和空间调节，目前仅在分子水平上刚刚开始被理解。在这里，我们概述了p97与其辅因子相互作用的结构框架、与不同辅因子组装复合物的潜在新原理，以及疾病相关p97突变对辅因子结合的致病影响。
