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© Research
Publication : Journal of peptide science : an official publication of the European Peptide Society

Structural properties of orexins for activation of their receptors

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of peptide science : an official publication of the European Peptide Society - 01 Apr 2006

Lang M, Bufe B, De Pol S, Reiser O, Meyerhof W, Beck-Sickinger AG

Link to Pubmed [PMID] – 16138386

J. Pept. Sci. 2006 Apr;12(4):258-66

The closely related neuropeptides orexin A and orexin B mediate their actions, including the regulation of sleep and appetite, by the activation of the orexin 1 and 2 receptors. To elucidate the structural prerequisites for receptor activation and subtype selectivity, we performed multiple amino acid substitutions within the sequence of orexin A and human orexin B-(6-28)-peptide and analyzed their solution structures by CD spectroscopy and their activity at both receptors in Ca(2+) mobilization assays. For orexin A, we showed that the basic amino acids within the segment of residues 6-14 were important for the activation of both receptors. Furthermore, we showed that the restriction via disulfide bonds is not required to maintain the active structure of orexin A. The kink region of h orexin B has been shown to be important for Ox(2)R selectivity, which is not mediated by the restriction of the turn structure. Additionally, we showed that no particular secondary structure is required for receptor subtype selectivity.

https://www.ncbi.nlm.nih.gov/pubmed/16138386