Crystal structure and functional implication of the RUN domain of human NESCA  

作　　者：Qifan Sun Chuanhui Han Lan Liu Yizhi Wang Hongyu Deng Lin Bai Tao Jiang 

机构地区：[1]National Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [2]Graduate University of Chinese Academy of Sciences,Beijing 100039,China [3]Chinese Academy of Sciences Key Laboratory of Infection and Immunity,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

出　　处：《Protein & Cell》2012年第8期609-617,共9页蛋白质与细胞（英文版）

基　　金：supported financially by the National Natural Science Foundation of China(Grant Nos.31021062 and 31025009);the National Basic Research Program(973 Program)(No.2011CB910302).

摘　　要：NESCA,a newly discovered signaling adapter protein in the NGF-pathway,contains a RUN domain at its N-terminus.Here we report the crystal structure of the NESCA RUN domain determined at 2.0-Åresolution.The overall fold of the NESCA RUN domain comprises nine helices,resembling the RUN domain of RPIPx and the RUN1 domain of Rab6IP1.However,compared to the other RUN domains,the RUN domain of NESCA has significantly different surface electrostatic distributions at the putative GTPase-interacting interface.We demonstrate that the RUN domain of NESCA can bind H-Ras,a downstream signaling molecule of TrkA,with high affinity.Moreover,NESCA RUN can directly interact with TrkA.These results provide new insights into how NESCA participates in the NGF-TrkA signaling pathway.

关 键 词：NESCA RUN domain crystal structure TRKA RAS 

分 类 号：R73[医药卫生—肿瘤]