Wenchi Zhang1, Liang Wang2, Yijin Liu3, Ji-Wei Xu3, Guangyu Zhu4, Huaixing Cang3, Xuemei Li3, Mark Bartlam5, Kenneth Hensley6, Guangpu Li7, Zihe Rao5, Xuejun C. Zhang4
1National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
2University of Oklahoma,
3CAS - Institute of Biophysics
4Oklahoma Medical Research Foundation
5Nankai University;
6University of Toledo
7Non-aligned
Tóm tắt
Eukaryotic lanthionine synthetase C-like protein 1 (LanCL1) is homologous to prokaryotic lanthionine cyclases, yet its biochemical functions remain elusive. We report the crystal structures of human LanCL1, both free of and complexed with glutathione, revealing glutathione binding to a zinc ion at the putative active site formed by conserved GxxG motifs. We also demonstrate by in vitro affinity analysis that LanCL1 binds specifically to the SH3 domain of a signaling protein, Eps8. Importantly, expression of LanCL1 mutants defective in Eps8 interaction inhibits nerve growth factor (NGF)-induced neurite outgrowth, providing evidence for the biological significance of this novel interaction in cellular signaling and differentiation.
