Allen Mark D, Buchberger Alexander, Bycroft Mark
Centre for Protein Engineering, Medical Research Council, Hills Road, Cambridge CB2 2QH, United Kingdom.
J Biol Chem. 2006 Sep 1;281(35):25502-8. doi: 10.1074/jbc.M601173200. Epub 2006 Jun 28.
The AAA ATPase p97 is a ubiquitin-selective molecular machine involved in multiple cellular processes, including protein degradation through the ubiquitin-proteasome system and homotypic membrane fusion. Specific p97 functions are mediated by a variety of cofactors, among them peptide N-glycanase, an enzyme that removes glycans from misfolded glycoproteins. Here we report the three-dimensional structure of the aminoterminal PUB domain of human peptide N-glycanase. We demonstrate that the PUB domain is a novel p97 binding module interacting with the D1 and/or D2 ATPase domains of p97 and identify an evolutionary conserved surface patch required for p97 binding. Furthermore, we show that the PUB and UBX domains do not bind to p97 in a mutually exclusive manner. Our results suggest that PUB domain-containing proteins constitute a widespread family of diverse p97 cofactors.
AAA 型 ATP 酶 p97 是一种泛素选择性分子机器，参与多种细胞过程，包括通过泛素 - 蛋白酶体系统进行的蛋白质降解和同型膜融合。特定的 p97 功能由多种辅助因子介导，其中包括肽 N - 糖苷酶，一种从错误折叠的糖蛋白中去除聚糖的酶。在此，我们报道了人肽 N - 糖苷酶氨基末端 PUB 结构域的三维结构。我们证明 PUB 结构域是一种与 p97 的 D1 和/或 D2 ATP 酶结构域相互作用的新型 p97 结合模块，并确定了 p97 结合所需的进化保守表面区域。此外，我们表明 PUB 结构域和 UBX 结构域并非以相互排斥的方式结合 p97。我们的结果表明，含 PUB 结构域的蛋白质构成了一个广泛存在的、多样的 p97 辅助因子家族。
