Rasimas Joseph J, Dalessio Paula A, Ropson Ira J, Pegg Anthony E, Fried Michael G
Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Protein Sci. 2004 Jan;13(1):301-5. doi: 10.1110/ps.03319404.
O(6)-alkylguanine-DNA alkyltransferase (AGT) repairs pro-mutagenic O(6)-alkylguanine and O(4)-alkylthymine lesions in DNA. The alkylated form of the protein is not reactivated; instead, it is rapidly ubiquitinated and degraded. Here, we show that alkylation destabilizes the native fold of the protein by 0.5-1.2 kcal/mole and the DNA-binding function by 0.8-1.4 kcal/mole. On this basis, we propose that destabilization of the native conformational ensemble acts as a signal for ubiquitination.
O(6)-烷基鸟嘌呤-DNA烷基转移酶(AGT)可修复DNA中具有致突变性的O(6)-烷基鸟嘌呤和O(4)-烷基胸腺嘧啶损伤。该蛋白质的烷基化形式不会被重新激活;相反,它会迅速被泛素化并降解。在此,我们表明烷基化使蛋白质的天然折叠稳定性降低0.5 - 1.2千卡/摩尔,使DNA结合功能稳定性降低0.8 - 1.4千卡/摩尔。在此基础上,我们提出天然构象集合的不稳定作为泛素化的信号。