LEPTIN IS A 4-HELIX BUNDLE - SECONDARY STRUCTURE BY NMR

Leptin is a signaling protein that in its mutant has been associated w ith obesity and Type II diabetes. The lack of sequence similarity has precluded analogies based on structural resemblance to known systems. Backbone NMR signals for mouse leptin (C-13/N-15-labeled) have been as signed and its secondary structure reveals it to be a four-helix bundl e cytokine. Helix lengths and disulfide pattern are in agreement with leptin as a member of the short-helix cytokine family. A three-dimensi onal model was built verifying the mechanical consistency of the ident ified elements with a short-helix cytokine core. (C) 1997 Federation o f European Biochemical Societies.