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

doi:10.1530/JOE-14-0264

Review

. 2014 Oct;223(1):T9-23.

doi: 10.1530/JOE-14-0264. Epub 2014 Jul 25.

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

Frank Peelman¹, Lennart Zabeau¹, Kedar Moharana¹, Savvas N Savvides¹, Jan Tavernier²

Affiliations

¹ Department of Medical Protein ResearchFaculty of Medicine and Health Sciences, Flanders Institute for Biotechnology (VIB), Ghent University, A. Baertsoenkaai 3, 9000 Ghent, BelgiumUnit for Structural BiologyLaboratory for Protein Biochemistry and Biomolecular Engineering (L-ProBE), Ghent University, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium.
² Department of Medical Protein ResearchFaculty of Medicine and Health Sciences, Flanders Institute for Biotechnology (VIB), Ghent University, A. Baertsoenkaai 3, 9000 Ghent, BelgiumUnit for Structural BiologyLaboratory for Protein Biochemistry and Biomolecular Engineering (L-ProBE), Ghent University, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium jan.tavernier@vib-ugent.be.

PMID: 25063754
DOI: 10.1530/JOE-14-0264

Review

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

Frank Peelman et al. J Endocrinol. 2014 Oct.

. 2014 Oct;223(1):T9-23.

doi: 10.1530/JOE-14-0264. Epub 2014 Jul 25.

Authors

Frank Peelman¹, Lennart Zabeau¹, Kedar Moharana¹, Savvas N Savvides¹, Jan Tavernier²

Affiliations

¹ Department of Medical Protein ResearchFaculty of Medicine and Health Sciences, Flanders Institute for Biotechnology (VIB), Ghent University, A. Baertsoenkaai 3, 9000 Ghent, BelgiumUnit for Structural BiologyLaboratory for Protein Biochemistry and Biomolecular Engineering (L-ProBE), Ghent University, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium.
² Department of Medical Protein ResearchFaculty of Medicine and Health Sciences, Flanders Institute for Biotechnology (VIB), Ghent University, A. Baertsoenkaai 3, 9000 Ghent, BelgiumUnit for Structural BiologyLaboratory for Protein Biochemistry and Biomolecular Engineering (L-ProBE), Ghent University, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium jan.tavernier@vib-ugent.be.

PMID: 25063754
DOI: 10.1530/JOE-14-0264

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.

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

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

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