Serine and threonine residues bend α-helices in the χ1 = g- conformation
Serine and threonine residues bend α-helices in the χ1 = g- conformation
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DOI：
10.1016/s0006-3495(00)76514-3
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发表时间：
2000-11-01
影响因子：
3.4
通讯作者：
Pardo, L
中科院分区：
文献类型：
--
作者：
Ballesteros, JA;Deupi, X;Pardo, L
已经在选择的包含α-螺旋的蛋白质结构中研究了Ser、Thr和Cys侧链构象（chi（1）= g（-），t，g（+））与主链构象（phi和psi角）之间的关系。统计结果表明，相对于Ala，Ser和Thr残基的g（-）构象使它们的phi角减小，而使它们的psi角增大。在Ser和Thr的O-γ原子与i-3或i-4肽羰基氧之间形成的额外氢键诱导或稳定螺旋中比Ala大3-4度的弯曲角。这对膜蛋白特别重要。在细胞膜一侧的跨膜α-螺旋中掺入这种小的弯曲角导致位于膜另一侧的残基的显著位移。我们推测，这些丝氨酸和苏氨酸残基的旋转异构体构型的局部改变可能会导致跨膜螺旋的显著构象变化，从而参与跨膜信号转导的分子机制。这一发现提供了结构基础，以了解实验观察到的影响丝氨酸残基的非活性和活性状态的受体之间的构象平衡，在神经递质亚家族的G蛋白偶联受体。
The relationship between the Ser, Thr, and Cys side-chain conformation (chi (1) = g(-), t, g(+)) and the main-chain conformation (phi and psi angles) has been studied in a selection of protein structures that contain alpha -helices. The statistical results show that the g(-) conformation of both Ser and Thr residues decreases their phi angles and increases their psi angles relative to Ala, used as a control. The additional hydrogen bond formed between the O-gamma atom of Ser and Thr and the i-3 or i-4 peptide carbonyl oxygen induces or stabilizes a bending angle in the helix 3-4 degrees larger than for Ala. This is of particular significance for membrane proteins. Incorporation of this small bending angle in the transmembrane alpha -helix at one side of the cell membrane results in a significant displacement of the residues located at the other side of the membrane. We hypothesize that local alterations of the rotamer configurations of these Ser and Thr residues may result in significant conformational changes across transmembrane helices, and thus participate in the molecular mechanisms underlying transmembrane signaling. This finding has provided the structural basis to understand the experimentally observed influence of Ser residues on the conformational equilibrium between inactive and active states of the receptor, in the neurotransmitter subfamily of G protein-coupled receptors.