Structure of human lanthionine synthetase C-like protein 1 and its interaction with Eps8 and glutathione.
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.
Zhang
Wenchi
W
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Wang
Liang
L
Liu
Yijin
Y
Xu
Jiwei
J
Zhu
Guangyu
G
Cang
Huaixing
H
Li
Xuemei
X
Bartlam
Mark
M
Hensley
Kenneth
K
Li
Guangpu
G
Rao
Zihe
Z
Zhang
Xuejun C
XC
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004926:Escherichia coli / Q000235:genetics; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D016716:PC12 Cells; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D015032:Zinc / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C489989:EPS8 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C485881:LANCL1 protein, human; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D020932:Nerve Growth Factor; D005978:Glutathione; D015032:Zinc