Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Science. 2013 Dec 6;342(6163):1235-9. doi: 10.1126/science.1243990.
Host cell factor-1 (HCF-1), a transcriptional co-regulator of human cell-cycle progression, undergoes proteolytic maturation in which any of six repeated sequences is cleaved by the nutrient-responsive glycosyltransferase, O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). We report that the tetratricopeptide-repeat domain of O-GlcNAc transferase binds the carboxyl-terminal portion of an HCF-1 proteolytic repeat such that the cleavage region lies in the glycosyltransferase active site above uridine diphosphate-GlcNAc. The conformation is similar to that of a glycosylation-competent peptide substrate. Cleavage occurs between cysteine and glutamate residues and results in a pyroglutamate product. Conversion of the cleavage site glutamate into serine converts an HCF-1 proteolytic repeat into a glycosylation substrate. Thus, protein glycosylation and HCF-1 cleavage occur in the same active site.
宿主细胞因子-1（HCF-1）是人类细胞周期进程的转录共调节因子，其经历蛋白水解成熟过程，其中营养响应糖基转移酶、O-连接 N-乙酰葡萄糖胺（O-GlcNAc）转移酶（OGT）可切割任意六个重复序列。我们报告称，O-GlcNAc 转移酶的四肽重复结构域结合 HCF-1 蛋白水解重复序列的羧基末端部分，使得切割区域位于尿苷二磷酸-GlcNAc 上方的糖基转移酶活性位点。构象类似于具有糖基化能力的肽底物。切割发生在半胱氨酸和谷氨酸残基之间，产生焦谷氨酸产物。将切割位点谷氨酸突变为丝氨酸可将 HCF-1 蛋白水解重复序列转化为糖基化底物。因此，蛋白质糖基化和 HCF-1 切割发生在相同的活性位点。
