Biochemistry, Biophysics, and Structural Biology Commons^™

Fus-Nls/Transportin 1 Complex Structure Provides Insights Into The Nuclear Targeting Mechanism Of Fus And The Implications In Als, Chunyan Niu, Jiayu Zhang, Feng Gao, Liuqing Yang, Minze Jia, Haining Zhu, Weimin Gong

Molecular and Cellular Biochemistry Faculty Publications

The C-terminal nuclear localization sequence of FUsed in Sarcoma (FUS-NLS) is critical for its nuclear import mediated by transportin (Trn1). Familial amyotrophic lateral sclerosis (ALS) related mutations are clustered in FUS-NLS. We report here the structural, biochemical and cell biological characterization of the FUS-NLS and its clinical implications. The crystal structure of the FUS-NLS/Trn1 complex shows extensive contacts between the two proteins and a unique α-helical structure in the FUS-NLS. The binding affinity between Trn1 and FUS-NLS (wide-type and 12 ALS-associated mutants) was determined. As compared to the wide-type FUS-NLS (K(D) = 1.7 nM), each ALS-associated mutation caused a decreased …