2rmh

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Human Urocortin 3

Overview

Members of the corticoliberin family include the corticotropin releasing, factors (CRFs), sauvagine, the urotensins, and urocortin 1 (Ucn1), which, bind to both the CRF receptors CRF-R1 and CRF-R2, and the urocortins 2, (Ucn2) and 3 (Ucn3), which are selective agonists of CRF-R2. Structure, activity relationship studies led to several potent and long-acting, analogues with selective binding to either one of the receptors. NMR, structures of six ligands of this family (the antagonists astressin B and, astressin2-B, the agonists stressin1, and the natural ligands human Ucn1, Ucn2, and Ucn3) were determined in DMSO. These six peptides show, differences in binding affinities, receptor-selectivity, and NMR, structure. Overall, their backbones are alpha-helical, with a small kink, or a turn around residues 25-27, resulting in a helix-loop-helix motif., The C-terminal helices are of amphipathic nature, whereas the N-terminal, helices vary in their amphipathicity. The C-terminal helices thereby, assume a conformation very similar to that of astressin bound to the ECD1, of CRF-R2 recently reported by our group.1 On the basis of an analysis of, the observed 3D structures and relative potencies of [Ala]-substituted, analogues, it is proposed that both helices could play a crucial role in, receptor binding and selectivity. In conclusion, the C-terminal helices, may interact along their hydrophobic faces with the ECD1, whereas the, entire N-terminal helical surface may be involved in receptor activation., On the basis of the common and divergent features observed in the 3D, structures of these ligands, multiple binding models are proposed that may, explain their plurality of actions.

About this Structure

2RMH is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

Reference

Common and divergent structural features of a series of corticotropin releasing factor-related peptides., Grace CR, Perrin MH, Cantle JP, Vale WW, Rivier JE, Riek R, J Am Chem Soc. 2007 Dec 26;129(51):16102-14. Epub 2007 Dec 6. PMID:18052377

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