3V6O

Leptin Receptor-antibody complex

Summary for 3V6O

• Entry DOI: 10.2210/pdb3v6o/pdb
• Descriptor: Leptin receptor, Monoclonal antibody 9F8 fab fragment Heavy chain, Monoclonal antibody 9F8 fab fragment Light chain, ... (9 entities in total)
• Functional Keywords: receptor-antibody complex, cytokine receptor, antibody fab fragment, immunoglobulin fold, leptin receptor-antibody complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 144456.21

Authors

Carpenter, B.,Hemsworth, G.R.,Ross, R.J.,Artymiuk, P.J. (deposition date: 2011-12-20, release date: 2012-03-14, Last modification date: 2024-10-16)

Primary citation

Carpenter, B.,Hemsworth, G.R.,Wu, Z.,Maamra, M.,Strasburger, C.J.,Ross, R.J.,Artymiuk, P.J.
Structure of the human obesity receptor leptin-binding domain reveals the mechanism of leptin antagonism by a monoclonal antibody.
Structure, 20:487-497, 2012

PubMed Abstract: Leptin regulates energy homeostasis, fertility, and the immune system, making it an important drug target. However, due to a complete lack of structural data for the obesity receptor (ObR), leptin's mechanism of receptor activation remains poorly understood. We have crystallized the Fab fragment of a leptin-blocking monoclonal antibody (9F8), both in its uncomplexed state and bound to the leptin-binding domain (LBD) of human ObR. We describe the structure of the LBD-9F8 Fab complex and the conformational changes in 9F8 associated with LBD binding. A molecular model of the putative leptin-LBD complex reveals that 9F8 Fab blocks leptin binding through only a small (10%) overlap in their binding sites, and that leptin binding is likely to involve an induced fit mechanism. This crystal structure of the leptin-binding domain of the obesity receptor will facilitate the design of therapeutics to modulate leptin signaling.

PubMed: 22405007
DOI: 10.1016/j.str.2012.01.019

Experimental method

X-RAY DIFFRACTION (1.95 Å)