Wu Ruoxi, Yue Yuan, Zheng Xiangdong, Li Haitao
MOE Key Laboratory of Protein Sciences, Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;
MOE Key Laboratory of Protein Sciences, Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China;
Genes Dev. 2015 Nov 15;29(22):2337-42. doi: 10.1101/gad.270926.115. Epub 2015 Nov 5.
NRMT1 is an N-terminal methyltransferase that methylates histone CENP-A as well as nonhistone substrates. Here, we report the crystal structure of human NRMT1 bound to CENP-A peptide at 1.3 Å. NRMT1 adopts a core methyltransferase fold that resembles DOT1L and PRMT but not SET domain family histone methyltransferases. Key substrate recognition and catalytic residues were identified by mutagenesis studies. Histone peptide profiling revealed that human NRMT1 is highly selective to human CENP-A and fruit fly H2B, which share a common "Xaa-Pro-Lys/Arg" motif. These results, along with a 1.5 Å costructure of human NRMT1 bound to the fruit fly H2B peptide, underscore the importance of the NRMT1 recognition motif.
NRMT1是一种N端甲基转移酶，可使组蛋白CENP-A以及非组蛋白底物发生甲基化。在此，我们报道了与CENP-A肽结合的人源NRMT1在1.3 Å分辨率下的晶体结构。NRMT1采用一种核心甲基转移酶折叠结构，该结构类似于DOT1L和PRMT，但不同于SET结构域家族组蛋白甲基转移酶。通过诱变研究确定了关键的底物识别和催化残基。组蛋白肽谱分析表明，人源NRMT1对人CENP-A和果蝇H2B具有高度选择性，它们共享一个共同的“Xaa-Pro-Lys/Arg”基序。这些结果，连同人源NRMT1与果蝇H2B肽结合的1.5 Å共结构，强调了NRMT1识别基序的重要性。
