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Orexin/hypocretin receptor chimaeras reveal structural features important for orexin peptide distinction
Author(s) -
Putula Jaana,
Turunen Pauli M.,
Johansson Lisa,
Näsman Johnny,
Ra Runar,
Korhonen Laura,
Kukkonen Jyrki P.
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.04.020
Subject(s) - receptor , orexin , orexin receptor , transmembrane domain , transmembrane protein , helix (gastropod) , orexin a , chemistry , g protein coupled receptor , peptide , ligand (biochemistry) , biology , biophysics , microbiology and biotechnology , biochemistry , neuropeptide , ecology , snail
We wanted to analyze the basis for the distinction between OX 1 and OX 2 orexin receptors by the known agonists, orexin‐A, orexin‐B and Ala 11 , d ‐Leu 15 ‐orexin‐B, of which the latter two show some selectivity for OX 2 . For this, chimaeric OX 1 /OX 2 and OX 2 /OX 1 orexin receptors were generated. The receptors were transiently expressed in HEK‐293 cells, and potencies of the agonists to elicit cytosolic Ca 2+ elevation were measured. The results show that the N‐terminal regions of the receptor are most important, and the exchange of the area from the C‐terminal part of the transmembrane helix 2 to the transmembrane helix 4 is enough to lead to an almost total change of the receptor's ligand profile.