Solution structure of a new hypothalamic neuropeptide, human hypocretin- 2/orexin-B

Jung Hoon Lee, Eunjung Bang, Kyeong Jun Chae, Jin Young Kim, Dai Woon Lee, Weontae Lee

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Orexin-A and orexin-B (also called hypocretin-1 and hypocretin-2, respectively) are novel hypothalamic neuropeptides encoded by a single mRNA transcript; they stimulate food intake. We have determined the three- dimensional solution structure of human hypocretin-2/orexin-B using two- dimensional 1H-NMR data and dynamical simulated annealing calculations. On the basis of NOEs, 3J(NHα) coupling constants and hydrogen-deuterium exchange rates together with chemical shift indices, human hypocretin- 2/orexin-B was deduced to consist of two α-helices connected with a short linker in both H2O and 30% trifluoroethanol solutions. The helical axis of helix I is oriented about 60-80°relative to helix II. Hybrid distance geometry and simulated-annealing protocols were used to generate an ensemble of 30 structures with no constraint violations greater than 0.03 nm for distances and 3°for angles. In addition, human hypocretin-2/orexin-B shares a similar secondary-structural motif with human neuropeptide Y. This result can form the basis for further study on ligand-receptor recognition of human orexin receptors.

Original languageEnglish
Pages (from-to)831-839
Number of pages9
JournalEuropean Journal of Biochemistry
Volume266
Issue number3
DOIs
Publication statusPublished - 1999 Dec 15

All Science Journal Classification (ASJC) codes

  • Biochemistry

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