Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
J Biol Chem. 2011 Sep 16;286(37):32251-8. doi: 10.1074/jbc.M111.254235. Epub 2011 Jul 13.
The defining feature of the α subunits of the family of nicotinic acetylcholine receptors is a vicinal disulfide between Cys-192 and Cys-193. Although this structure has played a pivotal role in a number of pioneering studies of nicotinic receptors, its functional role in native receptors remains uncertain. Using mutant cycle analysis and unnatural residue mutagenesis, including backbone mutagenesis of the peptide bond of the vicinal disulfide, we have established the presence of a network of hydrogen bonds that extends from that peptide NH, across a β turn to another backbone hydrogen bond, and then across the subunit interface to the side chain of a functionally important Asp residue in the non-α subunit. We propose that the role of the vicinal disulfide is to distort the β turn and thereby properly position a backbone NH for intersubunit hydrogen bonding to the key Asp.
家族烟碱型乙酰胆碱受体的 α 亚基的特征是半胱氨酸-192 和半胱氨酸-193 之间的毗邻二硫键。尽管这种结构在许多烟碱受体的开创性研究中发挥了关键作用，但它在天然受体中的功能作用仍然不确定。使用突变体循环分析和非天然残基诱变，包括毗邻二硫键肽键的骨架诱变，我们已经确定存在一个氢键网络，该网络从该肽 NH 延伸，穿过β 转角到达另一个骨架氢键，然后穿过亚基界面到达非α 亚基中功能重要的 Asp 残基的侧链。我们提出，毗邻二硫键的作用是扭曲β 转角，从而正确定位亚基间氢键的肽 NH 以与关键的 Asp 形成氢键。
