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. Author manuscript; available in PMC: 2011 Nov 19.

Published in final edited form as: J Mol Biol. 2010 Sep 8;404(1):45–55. doi: 10.1016/j.jmb.2010.08.054

A) Model of ASIP (red) docked to the extracellular domain of MC1R (blue with cyan extracellular loops), developed by Chai et al.³⁹ Data presented here demonstrate the importance of the ASIP C-terminal loop in MC1R recognition. We propose that the C-terminal loop interacts with EC1 through hydrophobic contacts (non-polar side chains are in white; Ala residues are not shown). In addition, R109 from the MC1R EC1 is positioned to form a salt bridge with ASIP D109, providing further stabilization. Coordinates, kindly provided by H. Mosberg and I. Pogozheva, are available at http://mosberglab.phar.umich.edu/resources/index.php. B) Schematic of ASIP-MC1R vs AgRP-MC4R interactions. Whereas AgRP requires only its N-terminal (N) and active (A) loops, ASIP also requires its C-terminal loop (C), to favor the non-signaling receptor state. With an altered (dashed lines) or missing ASIP C-terminal loop, ASIP functions as an agonist.

A) Model of ASIP (red) docked to the extracellular domain of MC1R (blue with cyan extracellular loops), developed by Chai et al.³⁹ Data presented here demonstrate the importance of the ASIP C-terminal loop in MC1R recognition. We propose that the C-terminal loop interacts with EC1 through hydrophobic contacts (non-polar side chains are in white; Ala residues are not shown). In addition, R109 from the MC1R EC1 is positioned to form a salt bridge with ASIP D109, providing further stabilization. Coordinates, kindly provided by H. Mosberg and I. Pogozheva, are available at http://mosberglab.phar.umich.edu/resources/index.php. B) Schematic of ASIP-MC1R vs AgRP-MC4R interactions. Whereas AgRP requires only its N-terminal (N) and active (A) loops, ASIP also requires its C-terminal loop (C), to favor the non-signaling receptor state. With an altered (dashed lines) or missing ASIP C-terminal loop, ASIP functions as an agonist.