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2
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1
Isomerization of the proline in the M2-M3 linker is not required for activation of the human 5-HT3A receptor.M2-M3连接子中脯氨酸的异构化对于人5-HT3A受体的激活并非必需。
J Neurochem. 2009 Aug;110(3):870-8. doi: 10.1111/j.1471-4159.2009.06180.x. Epub 2009 May 18.
2
X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation.处于明显开放构象的五聚体配体门控离子通道的X射线结构。
Nature. 2009 Jan 1;457(7225):111-4. doi: 10.1038/nature07462. Epub 2008 Nov 5.
3
Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel.质子激活的五聚体配体门控离子通道潜在开放状态的结构
Nature. 2009 Jan 1;457(7225):115-8. doi: 10.1038/nature07461. Epub 2008 Nov 5.
4
An intersubunit hydrogen bond in the nicotinic acetylcholine receptor that contributes to channel gating.烟碱型乙酰胆碱受体中有助于通道门控的亚基间氢键。
J Biol Chem. 2008 Dec 19;283(51):35638-43. doi: 10.1074/jbc.M807226200. Epub 2008 Oct 24.
5
A conserved salt bridge critical for GABA(A) receptor function and loop C dynamics.一个对GABA(A)受体功能和C环动力学至关重要的保守盐桥。
Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13604-9. doi: 10.1073/pnas.0801854105. Epub 2008 Aug 29.
6
X-ray structure of a prokaryotic pentameric ligand-gated ion channel.原核五聚体配体门控离子通道的X射线结构
Nature. 2008 Mar 20;452(7185):375-9. doi: 10.1038/nature06717. Epub 2008 Mar 5.
7
Acetylcholine receptor gating at extracellular transmembrane domain interface: the cys-loop and M2-M3 linker.细胞外跨膜结构域界面处的乙酰胆碱受体门控:半胱氨酸环和M2-M3连接区
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8
Improved amber and opal suppressor tRNAs for incorporation of unnatural amino acids in vivo. Part 1: minimizing misacylation.用于体内掺入非天然氨基酸的改良琥珀色和乳白抑制性tRNA。第1部分:将错误酰化降至最低。
RNA. 2007 Oct;13(10):1703-14. doi: 10.1261/rna.666807. Epub 2007 Aug 13.
9
Improved amber and opal suppressor tRNAs for incorporation of unnatural amino acids in vivo. Part 2: evaluating suppression efficiency.用于体内掺入非天然氨基酸的改良琥珀色和乳白抑制性tRNA。第2部分:评估抑制效率。
RNA. 2007 Oct;13(10):1715-22. doi: 10.1261/rna.667607. Epub 2007 Aug 13.
10
Crystal structure of the extracellular domain of nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution.分辨率为1.94埃时,与α-银环蛇毒素结合的烟碱型乙酰胆碱受体α1亚基细胞外结构域的晶体结构。
Nat Neurosci. 2007 Aug;10(8):953-62. doi: 10.1038/nn1942. Epub 2007 Jul 22.

Cys 环受体 Cys 环中 Phe-Pro 保守基序的化学尺度研究。

Chemical scale studies of the Phe-Pro conserved motif in the cys loop of Cys loop receptors.

机构信息

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.

出版信息

J Biol Chem. 2010 Mar 19;285(12):8976-84. doi: 10.1074/jbc.M109.060939. Epub 2010 Jan 12.

DOI:10.1074/jbc.M109.060939
PMID:20068044
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2838319/
Abstract

The functions of two conserved residues, Phe(135) and Pro(136), located at the apex of the Cys loop of the nicotinic acetylcholine receptor are investigated. Both residues were substituted with natural and unnatural amino acids, focusing on the role of aromaticity at Phe(135), backbone conformation at Pro(136), side chain polarity and volume, and the specific interaction between the aromatic side chain and the proline. NMR spectroscopy studies of model peptides containing proline and unnatural proline analogues following a Phe show a consistent increase in the population of the cis conformer relative to peptides lacking the Phe. In the receptor, a strong interaction between the Phe and Pro residues is evident, as is a strong preference for aromaticity and hydrophobicity at the Phe site. A similar influence of hydrophobicity is observed at the proline site. In addition, across a simple homologous series of proline analogues, the results reveal a correlation between receptor function and cis bias at the proline backbone. This could suggest a significant role for the cis proline conformer at this site in receptor function.

摘要

研究了位于烟碱型乙酰胆碱受体 Cys 环顶点的两个保守残基 Phe(135)和 Pro(136)的功能。用天然和非天然氨基酸取代了这两个残基,重点研究了 Phe(135)的芳香性、Pro(136)的主链构象、侧链极性和体积以及芳香侧链与脯氨酸之间的特异性相互作用。对含有脯氨酸和非天然脯氨酸类似物的模型肽进行 NMR 光谱研究表明,与不含 Phe 的肽相比,顺式构象的比例明显增加。在受体中,Phe 和 Pro 残基之间存在很强的相互作用,并且 Phe 位点对芳香性和疏水性有很强的偏好。在脯氨酸位点也观察到类似的疏水性影响。此外,在简单的同系系列脯氨酸类似物中,结果显示受体功能与脯氨酸主链的顺式偏好之间存在相关性。这表明在受体功能中,该位点的顺式脯氨酸构象可能具有重要作用。