20 YEARS OF LEPTIN: Insights into signaling assemblies of the leptin receptor

    1. Jan Tavernier
    1. Department of Medical Protein Research, Faculty of Medicine and Health Sciences, Flanders Institute for Biotechnology (VIB), Ghent University, A. Baertsoenkaai 3, 9000 Ghent, Belgium
      1Unit for Structural Biology, Laboratory for Protein Biochemistry and Biomolecular Engineering (L-ProBE), Ghent University, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium
    1. Correspondence should be addressed to J Tavernier; Email: jan.tavernier{at}vib-ugent.be


    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.

    • Received in final form 18 July 2014
    • Accepted 24 July 2014
    • Made available online as an Accepted Preprint 25 July 2014
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