Key result
U-II and URP bind UT extracellular loops II and III whereas urantide binds only loop II.
Why the study?
The conformational arrangement of UT receptor extracellular loops and transmembrane domains involved in ligand recognition was not fully characterized.
Answers are grounded in this paper and cite their sources.
U-II and URP share a common binding pattern to extracellular loops II and III of the UT receptor, distinct from the antagonist urantide which binds only loop II.
Urotensin-II (U-II) and urotensin-II-related peptide (URP) are potent vasoconstrictors, and this action is mediated through a G protein-coupled receptor identified as UT. This receptor is expressed abundantly in the mammalian cardiovasculature, and the effects of U-II and URP can be blocked with urantide, a selective antagonist. Thus, we carried out a study with the aim to characterize the conformational arrangement of the three extracellular loops of UT as well as the transmembrane domains III and IV. Secondary structures of the synthetic receptor fragments were determined using circular dichroism (CD) spectroscopy in a variety of solvent and micelle conditions. Spectra showed that all receptor segments but not the extracellular loop I exhibited a propensity for adopting the alpha-helix folding. Furthermore, using surface plasmon resonance (SPR) technology, we measured the binding affinities of the ligands, U-II, URP, and urantide toward the UT extracellular segments. SPR data showed that both U-II and URP bind extracellular loops II and III with similar affinities, whereas none of these two ligands were able to interact with the extracellular loop I. Moreover, the binding of urantide was observed only with the second extracellular loop. These results imply that U-II and URP but not urantide would bind to UT according to a common pattern. Also, the correlation of the CD spectral information with the affinity data suggested that the adoption of a helical geometry in UT, by extracellular loops II and III, might be essential for favoring the binding of ligands.
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Boivin et al. (2006) studied this question. U-II, URP, and urantide was evaluated on Binding affinities and secondary structures of UT extracellular segments. U-II and URP bind to extracellular loops II and III of the UT receptor with similar affinities, whereas urantide binds only to the second extracellular loop.
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