Structure of human lanthionine synthetase C-like protein 1 and its interaction with Eps8 and glutathione

  1. Wenchi Zhang1,6,
  2. Liang Wang2,6,
  3. Yijin Liu1,6,
  4. Jiwei Xu1,
  5. Guangyu Zhu3,
  6. Huaixing Cang1,
  7. Xuemei Li1,
  8. Mark Bartlam4,
  9. Kenneth Hensley5,7,
  10. Guangpu Li2,
  11. Zihe Rao1,4,8 and
  12. Xuejun C. Zhang1,3,9
  1. 1National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
  2. 2Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA;
  3. 3Protein Studies Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA;
  4. 4College of Life Sciences and Tianjin Key Laboratory of Protein Science, Nankai University, Tianjin 300071, China;
  5. 5Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA

    1. ↵6 These authors contributed equally to this work.

    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.

    Keywords

    Footnotes

    • ↵7 Present address: Department of Pathology, MS 1090, University of Toledo, Health Sciences Campus, 3000 Arlington Ave., Toledo, OH 43614, USA.

    • ↵8 Corresponding authors.

      E-MAIL raozh{at}xtal.tsinghua.edu.cn; FAX 86-10-62773145.

    • ↵9 E-MAIL zhangc{at}omrf.org; FAX (405) 271-7543.

    • Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1789209.

    • Supplemental material is available at http://www.genesdev.org.

      • Received February 6, 2009.
      • Accepted May 4, 2009.
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    1. doi: 10.1101/gad.1789209 Genes & Dev. 23: 1387-1392

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