2kza | pdb_00002kza

Solution structure of ASIP(80-132, P103A, P105A, Q115Y, S124Y)

spinqualitylabelsall models 2kza, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2kza is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 1y7j, 1y7k, 1mr0, 1hyk Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Agouti-related protein (AgRP) and agouti signaling protein (ASIP) are homologs that play critical roles in energy balance and pigmentation, respectively, by functioning as antagonistic ligands at their cognate melanocortin receptors. Signaling specificity is mediated in part through receptor binding selectivity brought about by alterations in the cysteine-rich carboxy-terminal domains of the ligands. AgRP binds with high affinity to the melanocortin 3 receptor and the melanocortin 4 receptor, but not to the melanocortin 1 receptor (MC1R), whereas ASIP binds with high affinity to all three receptors. This work explores the structural basis for receptor selectivity by studying chimeric proteins developed by interchanging loops between the cysteine-rich domain of ASIP and the cysteine-rich domain of AgRP. Binding data demonstrate that melanocortin 4 receptor responds to all chimeras and is therefore highly tolerant of gross loop changes. By contrast, MC1R responds primarily to those chimeras with a sequence close to that of wild-type ASIP. Further analysis of binding and functional data suggests that the ASIP C-terminal loop (a six-amino-acid segment closed by the final disulfide bond) is essential for high-affinity MC1R binding and inverse agonism. Comparison with previously published molecular models suggests that this loop makes contact with the first extracellular loop of MC1R through a series of key hydrophobic interactions. Loop-Swapped Chimeras of the Agouti-Related Protein and the Agouti Signaling Protein Identify Contacts Required for Melanocortin 1 Receptor Selectivity and Antagonism.,Patel MP, Cribb Fabersunne CS, Yang YK, Kaelin CB, Barsh GS, Millhauser GL J Mol Biol. 2010 Sep 8. PMID:20831872 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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