Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-5175
Zou, C; Kumaran, S; Markovic, S; Walser, R; Zerbe, O (2008). Studies of the Structure of the N-Terminal domain from the Y4 receptor - a G protein-coupled receptor - and its Interaction with hormones from the NPY family. ChemBioChem, 9(14):2276-2284.
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Binding of peptide hormones to G protein-coupled receptors is believed to be mediated through formation of contacts of the ligands with residues of the extracellular loops of family 1 GPCRs. Here we have investigated whether additional binding sites exist within the N-terminal domain, as studied in the form of binding of peptides from the neuropeptide Y (NPY) family to the N terminus of the Y4 receptor (N-Y4). The N-terminal domain of the Y4 receptor has been expressed in isotopically enriched form and studied by solution NMR spectroscopy. The peptide is unstructured in solution, whereas a micelle-associated helical segment is formed in the presence of dodecylphosphocholine (DPC) or sodium dodecylsulfate (SDS). As measured by surface plasmon resonance (SPR) spectroscopy, N-Y4 binds with approximately 50 M affinity to the pancreatic polypeptide (PP), a high-affinity ligand to the Y4 receptor, whereas binding to neuropeptide Y (NPY) and peptide YY (PYY) is much weaker. Residues critical for binding in PP and in N-Y4 have been identified by site-directed mutagenesis. The data indicate that electrostatic interactions dominate and that this interaction is mediated by acidic ligand and basic receptor residues. Residues of N-Y4 are likely to contribute to the binding of PP, and in addition might possibly also help to transfer the hormone from the membrane-bound state into the receptor binding pocket.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||07 Faculty of Science > Department of Chemistry|
|Uncontrolled Keywords:||GPCR Y receptor NMR structural biology interactions|
|Date:||2 September 2008|
|Deposited On:||17 Nov 2008 11:53|
|Last Modified:||05 Jun 2014 13:08|
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