Comparison of R128Q mutations in human, ovine, and chicken leptins

Nina Raver, Eyal Vardy, Oded Livnah, Rene Devos, Arieh Gertler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Human leptin and its R128Q mutant, as well as the R128Q mutants of ovine and chicken leptins, were prepared, expressed in Escherichia coli, refolded, and purified to homogeneity yielding electrophoretically pure, over 95% monomeric protein. R128Q mutations did not change the binding properties to BAF/3 cells stably transfected with the long form of human leptin receptor compared, respectively, to nonmutated human, ovine, and chicken leptins. In contrast, the biological activity tested in a proliferation assay in the same cells was drastically changed. Human leptin R128Q lost its activity and even became a weak antagonist, whereas the activities of ovine and chicken leptins were reduced 25- and 80-fold. If dimerization models were applicable leptin receptor activation, the present results would suggest that site 2 of the hormone was impaired. Two models, the human growth hormone:human growth hormone receptor (hGH: hGHR) (1:2) and the granulocyte-colony stimulating factor:granulocyte-colony stimulating factor receptor (GCSF:GCSFR) (2:2) complexes, were used for modeling. Superimposing the leptin structure on the hGH and GCSF models in the complex structures did not indicate any role for R128 in receptor binding. This made it impossible to correlate the results shown in the present work with the currently available models. Therefore, leptin may bind its receptors in a manner different than those proposed until now.

Original languageAmerican English
Pages (from-to)52-58
Number of pages7
JournalGeneral and Comparative Endocrinology
Issue number1
StatePublished - 2002


  • Chicken
  • Human
  • Leptin mutants
  • Ovine


Dive into the research topics of 'Comparison of R128Q mutations in human, ovine, and chicken leptins'. Together they form a unique fingerprint.

Cite this