The hydrophobic amino acids in putative helix 8 in carboxy-terminus of histamine H3 receptor are involved in receptor-G-protein coupling

2011 ◽  
Vol 23 (11) ◽  
pp. 1843-1849 ◽  
Author(s):  
Atsuo Kuramasu ◽  
Jun Sukegawa ◽  
Takeya Sato ◽  
Eiko Sakurai ◽  
Takehiko Watanabe ◽  
...  
Keyword(s):  
Amino Acids ◽  
G Protein ◽  
Carboxy Terminus ◽  
G Protein Coupling ◽  
Histamine H3 Receptor ◽  
Protein Coupling ◽  
H3 Receptor ◽  
Hydrophobic Amino Acids ◽  
Histamine H3

Differential expression and signaling of the human histamine H3 receptor isoforms of 445 and 365 amino acids expressed in human neuroblastoma SH-SY5Y cells

2018 ◽  
Vol 38 (2) ◽  
pp. 141-150 ◽  
Author(s):  
Gustavo Nieto-Alamilla ◽  
Juan Escamilla-Sánchez ◽  
María-Cristina López-Méndez ◽  
Anayansi Molina-Hernández ◽  
Agustín Guerrero-Hernández ◽  
...  
Keyword(s):  
Amino Acids ◽  
Differential Expression ◽  
Human Neuroblastoma ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Receptor Isoforms ◽  
Human Histamine ◽  
Histamine H3

G Protein-Dependent Pharmacology of Histamine H3 Receptor Ligands: Evidence for Heterogeneous Active State Receptor Conformations

2005 ◽  
Vol 314 (1) ◽  
pp. 271-281 ◽  
Author(s):  
Kathleen M. Krueger ◽  
David G. Witte ◽  
Lynne Ireland-Denny ◽  
Thomas R. Miller ◽  
John L. Baranowski ◽  
...  
Keyword(s):  
G Protein ◽  
Active State ◽  
Receptor Ligands ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

scholarly journals The role of the third intracellular loop of the neutrophil N-formyl peptide receptor in G protein coupling

1993 ◽  
Vol 294 (2) ◽  
pp. 581-587 ◽  
Author(s):  
E R Prossnitz ◽  
O Quehenberger ◽  
C G Cochrane ◽  
R D Ye
Keyword(s):  
Amino Acids ◽  
G Protein ◽  
Formyl Peptide Receptor ◽  
Wild Type ◽  
Intracellular Loop ◽  
G Protein Coupling ◽  
Protein Coupling ◽  
The Third ◽  
Third Intracellular Loop ◽  
Formyl Peptide

The G-protein-coupled N-formyl peptide receptor (FPR) contains one of the smallest known third intracellular loops of this class of receptors, consisting of only 15 amino acids. To study the role of this region of the receptor in G protein coupling and signal transduction, we generated a deletion mutant (D3i) in which 10 amino acids of the loop were removed, as well as a series of site-directed mutants containing substitutions of the charged and polar amino acids of this loop. The D3i mutant, expressed at normal levels on the cell surface, displayed a KD for labelled N-formyl-Met-Leu-Phe ([3H]FMLP) of 165 nM. This value compares with a KD for the wild-type FPR of 1.0 nM, or 20 nM in the presence of guanosine 5′-[gamma-thio]triphosphate, which uncouples G proteins from the receptor. These results indicate that D3i contains significant structural defects, beyond the disruption of G protein coupling, that affect ligand binding properties. Ten site-directed mutants generated in the third intracellular loop (T226A, K227E, H229A, K230Q, K235Q, S236A, S236A/S237G, R238G, R241E and S244A) displayed KD values between 0.5 and 1.0 nM, with expression levels between 22% (K227E) and 111% (H229A) of that of wild type receptor. The capacity of the mutants for signal transductions was determined by measuring intracellular Ca2+ mobilization. Eight of the ten mutants displayed EC50 values for FMLP of between 0.07 and 0.9 nM, as compared with 0.12 nM for the wild-type receptor. The two mutants K227E and R238G had EC50 values of 2.7 and 2.9 nM respectively. The increase in EC50 could be accounted for partially by the low levels of receptor expression. All ten mutants gave maximum levels of Ca2+ mobilization similar to that produced by the wild-type FPR. These results contradict the conclusions reached with other G-protein-coupled receptors and indicate that the third intracellular loop of the FPR does not have a critical role in the functional coupling of G proteins.

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