Discovering Targetable Conformation of RhoA Mutant by Integrating Native Mass Spectrometry, Ultraviolet Photodissociation, and X-ray Diffraction.

doi:10.1021/jacs.5c20067

Article

Discovering Targetable Conformation of RhoA Mutant by Integrating Native Mass Spectrometry, Ultraviolet Photodissociation, and X-ray Diffraction.

Journal of the American Chemical Society - 25 Mar 2026

Wu Haozhe, Liu Zheyi, Jiang Hao, Zhao Heng, Dong Chen, Lu Yu, Zu Shijia, Guo Yongjie, Lai Can, Luo Pan, Xu Ke, Yang Yuxin, Yang Yafang, Sun Zhongya, Huang Qingcheng, Xiong Huan, Zhou Lanxin, Luo Yipan, Zeng Yuhan, Du Daohai, Liang Zhongjie, Xiao Weilie, Zhao Shan, Zhang Weiqing, Tang Yong, Xiao Chunlei, Chen Kaixian, Yang Xueming, Wang Fangjun, Luo Cheng

Abstract excerpt

Pathogenic mutations in "undruggable" Ras superfamily proteins challenge drug development by inducing subtle, dynamic conformational changes. Here, we integrated X-ray crystallography with native mass spectrometry and ultraviolet photodissociation (nMS-UVPD) to reveal a cryptic conformation in the oncogenic Y42C mutant of RhoA. While crystallography alone resolved two ambiguous structures, nMS-UVPD determined the...

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Discovering Targetable Conformation of RhoA Mutant by Integrating Native Mass Spectrometry, Ultraviolet Photodissociation, and X-ray Diffraction.

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