4.7 Article

Residues in the 1st Transmembrane-Spanning Helix Are Important for GABAAρ Receptor Function

期刊

BIOMOLECULES
卷 12, 期 9, 页码 -

出版社

MDPI
DOI: 10.3390/biom12091251

关键词

Cys-loop receptor; binding site; mutagenesis; aromatic interaction; hydrophobic interaction

资金

  1. Astra-Zeneca studentship
  2. M.R.C. [MR/L021676/1]
  3. University of Cambridge

向作者/读者索取更多资源

This study identified the important M1 residues in GABA(A rho) receptors using mutagenesis and functional assays. The results provide insights into the functional properties of these residues and their differences among subunits. These findings are significant for understanding the mechanism of GABA(A rho) receptor function.
GABA(A rho )receptors are a subfamily of the GABA(A) receptor family of pentameric ligand-gated ion channels (pLGICs). Each subunit has a common structure, including a transmembrane domain of four alpha-helices (M1-M4). The aim of this study was to identify important M1 residues in the GABA(A rho )receptor (GABA(A rho)R), using mutagenesis and functional assays combined with bioinformatic approaches. Alanine substitution of 12 of the 23 M1 residues yielded receptors with altered functional parameters, indicating these residues contribute to GABA(A rho)R function. Further mutations reveal the properties that are important for function in critical residues, and, using a GABA(A rho)R homology model, we suggest amino acid interactions that could be important. Phylogenetic analysis comparing GABA(A rho)R and other pLGICs subunits reveals most M1 residue properties linked to GABA(A rho)R function are ancestrally ancient, but some are more recent acquisitions. Multiple sequence alignment of M1 residues across GABA(A rho)R subunits reveal three residues are well conserved except in GABA(A rho)R alpha subunits. Substitution of rho 1 subunit residues to their alpha 1 subunit equivalents showed one alters functional parameters. Overall, the data provide a comprehensive picture of M1 residues that contribute to GABA(A rho)R function, and illustrate how they might do so.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据