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. 2020 Sep 1;12(9):741-744.
doi: 10.1093/jmcb/mjaa025.

Molecular basis for the functions of dominantly active Y35N and inactive D60K Rheb mutants in mTORC1 signaling

Chunxiao Zhang  1 , Yan Liu  2 , Yifang Zhang  1 , Xiangxiang Wang  3 , Tianlong Zhang  1 , Jianping Ding  1   4
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Molecular basis for the functions of dominantly active Y35N and inactive D60K Rheb mutants in mTORC1 signaling

Chunxiao Zhang et al. J Mol Cell Biol. .
No abstract available

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Figures

Figure 1
Figure 1
Crystal structures and biochemical characterization of Rheb Y35N and D60K mutants. (A and B) In vitro kinase activity assays of mTORC1 toward S6K1 phosphorylation in the absence or presence of Rheb WT, Y35N (A), or D60K (B). Band intensities for p-S6K1 are quantified and presented as graphs in the upper panel. The gels for the inputs were stained with Coomassie blue. (C) Overall structures of Y35NGppNHp, Y35NGDP, and D60KGDP. The switch I region is colored in green, the switch II region in blue, the interswitch region in cyan, and the other part of Rheb in wheat. Mg2+ is shown as a sphere in magenta, and the nucleotide with a ball-and-stick model in yellow. (D) Interactions between the switch I regions of WT and mutant Rheb with mTOR. The structure models are constructed by superimposing the structures of WTGppNHp (PDB code 1XTR), WTGDP (PDB code 1XTQ), Y35NGppNHp, Y35NGDP, D60KGDP, and Y35AGDP (PDB code 3SEA) onto the structure of WT Rheb in the cryo-EM structure of Rheb‒mTORC1 complex (PDB code 6BCU). The residues involved in the interactions are shown with ball-and-stick models and colored as in C.
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