Open AccessSolution structure of a new hypothalamic neuropeptide, human hypocretin‐2/orexin‐B
Author(s) -
Lee JungHoon,
Bang Eunjung,
Chae KyeongJun,
Kim JinYoung,
Lee Dai Woon,
Lee Weontae
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00911.x
Subject(s) - orexin , orexin a , neuropeptide , chemistry , receptor , orexin receptor , crystallography , biophysics , biochemistry , biology
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 1 H‐NMR data and dynamical simulated annealing calculations. On the basis of NOEs, 3 J HNα 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 H 2 O 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.