20 years of leptin: insights into signaling assemblies of the leptin receptor

J Endocrinol. 2014 Oct;223(1):T9-23. doi: 10.1530/JOE-14-0264. Epub 2014 Jul 25.

Abstract

Leptin plays a central role in the control of body weight and energy homeostasis, but is a pleiotropic cytokine with activities on many peripheral cell types. In this review, we discuss the interaction of leptin with its receptor, and focus on the structural and mechanistic aspects of the extracellular aspects of leptin receptor (LR) activation. We provide an extensive overview of all structural information that has been obtained for leptin and its receptor via X-ray crystallography, electron microscopy, small-angle X-ray scattering, homology modeling, and mutagenesis studies. The available knowledge is integrated into putative models toward a recapitulation of the LR activation mechanism.

Keywords: leptin; leptin receptor; modeling; structure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Humans
  • Leptin / chemistry*
  • Leptin / genetics
  • Leptin / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary*
  • Receptors, Leptin / chemistry*
  • Receptors, Leptin / genetics
  • Receptors, Leptin / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction*

Substances

  • Leptin
  • Receptors, Leptin