Structure-function studies of human leptin

Keiichi Imagawa, Yoshito Numata, Goro Katsuura, Isako Sakaguchi, Atsushi Morita, Shino Kikuoka, Yayoi Matumoto, Tetsuo Tsuji, Mikio Tamaki, Kazuyuki Sasakura, Hiroshi Teraoka, Kiminori Hosoda, Yoshihiro Ogawa, Kazuwa Nakao

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Abstract

To elucidate the structural requirement of human leptin for its functions, the wild-type, mutant-type, C-terminal deletion, and N-terminal deletion were expressed in Escherichia coli and purified in soluble forms. These leptin analogs were intracerebroventrically injected into C57BL/6J ob/ob mice, and their in vivo biological activities were evaluated. The mutant-type leptin lacking a C-terminal disulfide bond reduced food intake at doses of more than 15 pmol/mouse, which was as effective as the wild-type leptin. C-terminal deletion without the loop structure, also significantly, but to a lesser extent, reduced food intake at doses of more than 90 pmol/mouse. However, N-terminal deletions showed no effect on food intake. We also evaluated the effects of the leptin analogs on radiolabeled leptin binding to its receptor in the choroid plexus using autoradiography. An excess of unlabeled mutant-type leptin as well as wild-type leptin led to complete inhibition of binding. C-terminal deletions led to weak inhibitory activity, whereas N-terminal deletions caused no inhibitory activity. These results clearly demonstrate that the N-terminal region of leptin is essential for both its biological and receptor binding activities. The amino acid sequence of the C-terminal loop structure is also important for enhancing these actions, whereas the C-terminal disulfide bond is not needed.

Original languageEnglish
Pages (from-to)35245-35249
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number52
DOIs
Publication statusPublished - Dec 25 1998
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Imagawa, K., Numata, Y., Katsuura, G., Sakaguchi, I., Morita, A., Kikuoka, S., ... Nakao, K. (1998). Structure-function studies of human leptin. Journal of Biological Chemistry, 273(52), 35245-35249. https://doi.org/10.1074/jbc.273.52.35245