The N‐terminal acidic residue of the cytosolic helix 8 of an odorant receptor is responsible for different response dynamics via G‐protein. Issue 10 (31st March 2015)

• Record Type: Journal Article
• Authors: Kawasaki, Takashi; Saka, Takahiro; Mine, Shouhei; Mizohata, Eiichi; Inoue, Tsuyoshi; Matsumura, Hiroyoshi; Sato, Takaaki
• Is Part Of: FEBS letters. Volume 589:Issue 10(2015)
• Page Start: 1136
• Page End: 1142
• Publication Date: 2015-03-31
• Subjects: Odorant receptor -- G-protein coupled receptor -- Mouse -- Ca2+ imaging -- Interaction -- Homology model; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2015.03.025
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : We previously observed highly rapid and robust response of murine olfactory receptor S6 (mOR‐S6) with chimeric Gα15_olf, compared to Gα15 . To identify residues responsible for this difference in response, mutations of the cytosolic helix 8 were analyzed in a heterologous functional expression system. The N‐terminal hydrophobic core between helix 8 and TM1–2 of mOR‐S6 is important for activation of both Gα15_olf and Gα15 . Point mutation of a helix 8 N‐terminal acidic residue eliminated the differences in response dynamics via Gα. This result suggests that an N‐terminal acidic residue of helix 8 is responsible for rapid response via Gα15_olf . Abstract : Residues responsible for improved Ca 2+ response dynamics by Gα15 _olf are unknown. We analyzed Ca 2+ responses of mutated mOR‐S6 helix 8 and created a homology model. The N‐terminal hydrophobic core of helix 8/TM1−2 is important for Gα activation. Mutations of the second residue of helix 8 eliminated different response dynamics. The second and fifth residues are responsible for improved responses by Gα15 _olf .