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Identification of critical residues in loop E in the 5-HT(3AS)R binding site
BACKGROUND: The serotonin type 3 receptor (5-HT(3)R) is a member of a superfamily of ligand gated ion channels. All members of this family share a large degree of sequence homology and presumably significant structural similarity. A large number of studies have explored the structure-function relati...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2002
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC117120/ https://www.ncbi.nlm.nih.gov/pubmed/12079500 http://dx.doi.org/10.1186/1471-2091-3-15 |
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author | Venkataraman, Padmavati Venkatachalan, Srinivasan P Joshi, Prasad R Muthalagi, Mani Schulte, Marvin K |
author_facet | Venkataraman, Padmavati Venkatachalan, Srinivasan P Joshi, Prasad R Muthalagi, Mani Schulte, Marvin K |
author_sort | Venkataraman, Padmavati |
collection | PubMed |
description | BACKGROUND: The serotonin type 3 receptor (5-HT(3)R) is a member of a superfamily of ligand gated ion channels. All members of this family share a large degree of sequence homology and presumably significant structural similarity. A large number of studies have explored the structure-function relationships of members of this family, particularly the nicotinic and GABA receptors. This information can be utilized to gain additional insights into specific structural and functional features of other receptors in this family. RESULTS: Thirteen amino acids in the mouse 5-HT(3AS)R that correspond to the putative E binding loop of the nicotinic α7 receptor were chosen for mutagenesis. Due to the presence of a highly conserved glycine in this region, it has been suggested that this binding loop is comprised of a hairpin turn and may form a portion of the ligand-binding site in this ion channel family. Mutation of the conserved glycine (G147) to alanine eliminated binding of the 5-HT(3)R antagonist [(3)H]granisetron. Three tyrosine residues (Y140, Y142 and Y152) also significantly altered the binding of 5-HT(3)R ligands. Mutations in neighboring residues had little or no effect on binding of these ligands to the 5-HT(3AS)R. CONCLUSION: Our data supports a role for the putative E-loop region of the 5-HT(3)R in the binding of 5-HT, mCPBG, d-tc and lerisetron. 5-HT and mCPBG interact with Y142, d-tc with Y140 and lerisetron with both Y142 and Y152. Our data also provides support for the hypothesis that this region of the receptor is present in a loop structure. |
format | Text |
id | pubmed-117120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-1171202002-07-12 Identification of critical residues in loop E in the 5-HT(3AS)R binding site Venkataraman, Padmavati Venkatachalan, Srinivasan P Joshi, Prasad R Muthalagi, Mani Schulte, Marvin K BMC Biochem Research Article BACKGROUND: The serotonin type 3 receptor (5-HT(3)R) is a member of a superfamily of ligand gated ion channels. All members of this family share a large degree of sequence homology and presumably significant structural similarity. A large number of studies have explored the structure-function relationships of members of this family, particularly the nicotinic and GABA receptors. This information can be utilized to gain additional insights into specific structural and functional features of other receptors in this family. RESULTS: Thirteen amino acids in the mouse 5-HT(3AS)R that correspond to the putative E binding loop of the nicotinic α7 receptor were chosen for mutagenesis. Due to the presence of a highly conserved glycine in this region, it has been suggested that this binding loop is comprised of a hairpin turn and may form a portion of the ligand-binding site in this ion channel family. Mutation of the conserved glycine (G147) to alanine eliminated binding of the 5-HT(3)R antagonist [(3)H]granisetron. Three tyrosine residues (Y140, Y142 and Y152) also significantly altered the binding of 5-HT(3)R ligands. Mutations in neighboring residues had little or no effect on binding of these ligands to the 5-HT(3AS)R. CONCLUSION: Our data supports a role for the putative E-loop region of the 5-HT(3)R in the binding of 5-HT, mCPBG, d-tc and lerisetron. 5-HT and mCPBG interact with Y142, d-tc with Y140 and lerisetron with both Y142 and Y152. Our data also provides support for the hypothesis that this region of the receptor is present in a loop structure. BioMed Central 2002-06-13 /pmc/articles/PMC117120/ /pubmed/12079500 http://dx.doi.org/10.1186/1471-2091-3-15 Text en Copyright © 2002 Venkataraman et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. |
spellingShingle | Research Article Venkataraman, Padmavati Venkatachalan, Srinivasan P Joshi, Prasad R Muthalagi, Mani Schulte, Marvin K Identification of critical residues in loop E in the 5-HT(3AS)R binding site |
title | Identification of critical residues in loop E in the 5-HT(3AS)R binding site |
title_full | Identification of critical residues in loop E in the 5-HT(3AS)R binding site |
title_fullStr | Identification of critical residues in loop E in the 5-HT(3AS)R binding site |
title_full_unstemmed | Identification of critical residues in loop E in the 5-HT(3AS)R binding site |
title_short | Identification of critical residues in loop E in the 5-HT(3AS)R binding site |
title_sort | identification of critical residues in loop e in the 5-ht(3as)r binding site |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC117120/ https://www.ncbi.nlm.nih.gov/pubmed/12079500 http://dx.doi.org/10.1186/1471-2091-3-15 |
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