The role of the C-terminus of the human hydroxycarboxylic acid receptors 2 and 3 in G protein activation using G_α-engineered yeast cells

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• 作者：Rongfang Liu ; Jacobus P.D. van Veldhoven ; Adriaan P. IJzerman ; ^{ijzerman@lacdr.leidenuniv.nl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：nicotinic acid (NA) ; pyridine-3-carboxylic acid (PubChem CID ; 938) ; acifran ; 5-methyl-4-oxo-5-phenylfuran-2-carboxylic acid (PubChem CID ; 51576) ; LUF7159 ; 5-(Bis-thiophen-3-ylmethyl-amino)-1H-pyrazole-3-carboxylic acid
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：5 January 2016
• 年：2016
• 卷：770
• 期：Complete
• 页码：70-77
• 全文大小：2122 K

文摘

In the present study we focused our attention on the family of hydroxycarboxylic acid (HCA) receptors, a GPCR family of three members, of which the HCA₂ and HCA₃ receptors share 95% high sequence identity but differ considerably in C-terminus length with HCA₃ having the longest tail. The two receptors were expressed and analysed for their activation profile in Saccharomyces cerevisiae MMY yeast strains that have different G protein G_α subunits. The hHCA₂ receptor was promiscuous in its G protein coupling preference. In the presence of nicotinic acid the hHCA₂ receptor activated almost all G protein pathways except G_αq (MMY14). However, the G_α protein coupling profile of the hHCA₃ receptor was less promiscuous, as the receptor only activated G_αi1 (MMY23) and G_αi3 (MMY24) pathways.

50">We then constructed two mutant receptors by ‘swapping’ the short (HCA₂) and long (HCA₃) C-terminus. The differences in HCA₂ and HCA₃ receptor activation and G protein selectivity were not controlled, however, by their C-terminal tails, as we observed only minor differences between mutant and corresponding wild-type receptor. This study provides new insights into the G protein coupling profiles of the HCA receptors and the function of the receptor's C terminus, which may be extended to other GPCRs.