Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Escherichia coli / genetics
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Gene Expression Regulation
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Glutathione / metabolism*
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism*
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Models, Molecular
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Mutation
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Nerve Growth Factor / pharmacology
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Neurites / physiology
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Neurons / cytology
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Neurons / drug effects
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PC12 Cells
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Protein Binding
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Protein Structure, Tertiary
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Rats
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Receptors, G-Protein-Coupled / chemistry*
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Signal Transduction
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Zinc / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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EPS8 protein, human
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Intracellular Signaling Peptides and Proteins
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LANCL1 protein, human
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Receptors, G-Protein-Coupled
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Recombinant Proteins
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Nerve Growth Factor
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Glutathione
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Zinc