Distinct association of HRAS and KRAS with Mn^(2+) ion illustrated by paramagnetic NMR  

作　　者：Jia-Liang Chen Xun-Cheng Su 

机构地区：[1]State Key Laboratory of Elemento-organic Chemistry,College of Chemistry,Nankai University,Tianjin,300071,China [2]College of Chemistry,Chemical Engineering and Materials Science,Zaozhuang University,Zaozhuang,277160,China

出　　处：《Magnetic Resonance Letters》2025年第1期22-31,共10页磁共振快报(英文)

基　　金：supported by the Ministry of Science and Technology of China(2021YFA1600304);the National Natural Science Foundation of China(22161142018,21991081,22174074 and 22374126).

摘　　要：Rat sarcoma virus oncogene(RAS)proteins are of crucial oncogenic proteins and are involved in several essential intracellular processes.The RAS protein has an intrinsic metal binding site for Mg^(2+),which is important for the conformational stability of the active site.Recently,it was reported that a second metal ion binding site,located further from the active site in HRAS(Harvey RAS homolog),binds Ca^(2+) with millimolar affinity.As one of the most abundant metal ions in cells,Mn^(2+) is a potential candidate for the second metal ion binding site in RAS proteins.Here,we examined the interaction of Mn^(2+) with HRAS and KRAS(Kirsten RAS homolog)using high resolution NMR spectroscopy.The NMR data showed that both the second metal ion binding site and the switch I and II regions bind Mn^(2+) in the RAS proteins.Furthermore,our paramagnetic NMR results disclosed the conformational differences in helix a3 and the following loop between HRAS and KRAS,accompanied by the association with metal ion binding.These results provide new insights into the interaction of RAS proteins and Mn^(2+) in the respective biological processes in cells.

关 键 词：HRAS KRAS Mn^(2+) NMR PRE 

分 类 号：R73[医药卫生—肿瘤]