Structure of human lanthionine synthetase C-like protein 1 and its interaction with Eps8 and glutathione
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.
Từ khóa
Tài liệu tham khảo
Landlinger, 2006, Myristoylation of human LanC-like Protein 2 (LANCL2) is essential for the interaction with the plasma membrane and the increase in cellular sensitivity to adriamycin, Biochim Biophys Acta, 1758, 1759, 10.1016/j.bbamem.2006.07.018
Mayer, 1998, Molecular characterization and tissue-specific expression of a murine putative G-protein-coupled receptor, Biochim Biophys Acta, 1399, 51, 10.1016/S0167-4781(98)00091-8