Structural highlights
Disease
[OREX_HUMAN] Defects in HCRT are the cause of narcolepsy type 1 (NRCLP1) [MIM:161400]. Narcolepsy is a neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep, such as cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy is a sudden loss of muscle tone triggered by emotions, which is the most valuable clinical feature used to diagnose narcolepsy. Human narcolepsy is primarily a sporadically occurring disorder but familial clustering has been observed. Note=Human narcolepsy is associated with a deficient orexin system. Orexins are absent and/or greatly diminished in the brain and cerebrospinal fluid (CSF) of most narcoleptic patients.[1]
Function
[OREX_HUMAN] Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested. Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity.
Publication Abstract from PubMed
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, 3JHNalpha coupling constants and hydrogen-deuterium exchange rates together with chemical shift indices, human hypocretin-2/orexin-B was deduced to consist of two alpha-helices connected with a short linker in both H2O and 30% trifluoroethanol solutions. The helical axis of helix I is oriented about 60-80 degrees 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 degrees 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.
Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B.,Lee JH, Bang E, Chae KJ, Kim JY, Lee DW, Lee W Eur J Biochem. 1999 Dec;266(3):831-9. PMID:10583376[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, Li R, Hungs M, Pedrazzoli M, Padigaru M, Kucherlapati M, Fan J, Maki R, Lammers GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000 Sep;6(9):991-7. PMID:10973318 doi:10.1038/79690
- ↑ Lee JH, Bang E, Chae KJ, Kim JY, Lee DW, Lee W. Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B. Eur J Biochem. 1999 Dec;266(3):831-9. PMID:10583376
