The polarity of lipid-exposed residues contributes to the functional differences between Torpedo and muscle-type nicotinic receptors.
The polarity of lipid-exposed residues contributes to the functional differences between Torpedo and muscle-type nicotinic receptors.
复制标题
脂质暴露残基的极性导致鱼雷型烟碱受体和肌肉型烟碱受体之间的功能差异。
DOI：
10.1007/s00232-006-0051-0
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Lasalde-Dominicci,JoséA
中科院分区：
文献类型：
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作者：
Guzmán,GisilaR;Ortiz-Acevedo,Alejandro;Ricardo,Ariamsi;Rojas,LegierV;Lasalde-Dominicci,JoséA
电鳐型和肌肉型乙酰胆碱受体（AChRs）之间的比较揭示了几种脂质暴露氨基酸的差异，特别是这些残基的极性。本研究的目的是描述8个暴露于脂质的残基在电鳐型和肌肉型AChRs之间的功能差异中的作用。为了达到这一目的，将电鳐AChR中的αS287、αC412、β Y 441、γM299、γS460、δM293、δS297和δN305残基替换为肌型受体中的残基。用[125 I]-α-银环蛇毒素检测异种卵母细胞AChR突变体受体表达，用双电极电压钳检测AChR离子通道功能。八个突变体组合导致AChR表达增加（1.5至5.2倍）。四个突变体组合产生了显着的乙酰胆碱的50%抑制浓度（EC 50）的46%的下降，而三个突变体组合导致乙酰胆碱的EC 50增加1.7至2倍。最后，七个突变体组合导致标准化，乙酰胆碱诱导的电流减少。我们的研究结果表明，这些残基，虽然远离离子通道孔，（1）有助于离子通道门控，（2）可能会影响AChR运输到专门的膜结构域和（3）帐户电鳐和肌肉型AChR之间的功能差异。这些发现强调了脂质-蛋白质界面在电鳐型和肌肉型AChRs功能差异中的重要性。
A comparison between theTorpedoand muscle-type acetylcholine receptors (AChRs) reveals differences in several lipid-exposed amino acids, particularly in the polarity of those residues. The goal of this study was to characterize the role of eight lipid-exposed residues in the functional differences between theTorpedoand muscle-type AChRs. To this end, residues αS287, αC412, βY441, γM299, γS460, δM293, δS297 and δN305 in theTorpedoAChR were replaced with those found in the muscle-type receptor. Mutant receptor expression was measured inXenopusoocytes using [125I]-α-bungarotoxin, and AChR ion channel function was evaluated using the two-electrode voltage clamp. Eight mutant combinations resulted in an increase (1.5- to 5.2-fold) in AChR expression. Four mutant combinations produced a significant 46% decrease in the ACh 50% inhibitory concentration (EC50), while three mutant combinations resulted in 1.7- to 2-fold increases in ACh EC50. Finally, seven mutant combinations resulted in a decrease in normalized, ACh-induced currents. Our results suggest that these residues, although remote from the ion channel pore, (1) contribute to ion channel gating, (2) may affect trafficking of AChR into specialized membrane domains and (3) account for the functional differences betweenTorpedoand muscle-type AChR. These findings emphasize the importance of the lipid-protein interface in the functional differences between theTorpedoand muscle-type AChRs.