From Static Structure to Living Protein: Computational Analysis of Cytochrome c Oxidase Main-chain Flexibility
From Static Structure to Living Protein: Computational Analysis of Cytochrome c Oxidase Main-chain Flexibility
复制标题
DOI：
10.1016/j.bpj.2012.03.040
复制
发表时间：
2012-05-02
影响因子：
3.4
通讯作者：
Kuhn, Leslie A.
中科院分区：
文献类型：
--
作者：
Buhrow, Leann;Ferguson-Miller, Shelagh;Kuhn, Leslie A.
晶体结构和氘的可及性比较CcO在不同的氧化还原状态，建议构象变化的机械意义。为了预测CcO的内在柔性和低能运动，这项工作分析了可用的高分辨率晶体结构与ProFlex和elNemo计算方法。结果确定灵活的区域和潜在的构象变化CcO相关以及与已发表的结构和生化数据，并提供机制的见解。预测CcO在膜的内部和外部经历旋转运动，由跨膜螺旋倾斜和弯曲驱动，再加上β-折叠结构域的摇摆。因此，质子K-途径变得足够灵活，内部水分子交替占据途径的上部和下部，与保守的Thr-359和Lys-362残基相关。发现D-途径螺旋是相对刚性的，具有涉及亚基I C-末端的高度灵活的入口区域，潜在地调节质子的摄取。RsCcO疏水通道的收缩和扩张表明双核中心的氧供应调节。这种分析指出，耦合CcO的构象变化和它们的潜力，影响质子和氧的访问。
Crystallographic structure and deuterium accessibility comparisons of CcO in different redox states have suggested conformational changes of mechanistic significance. To predict the intrinsic flexibility and low energy motions in CcO, this work has analyzed available high-resolution crystallographic structures with ProFlex and elNemo computational methods. The results identify flexible regions and potential conformational changes in CcO that correlate well with published structural and biochemical data and provide mechanistic insights. CcO is predicted to undergo rotational motions on the interior and exterior of the membrane, driven by transmembrane helical tilting and bending, coupled with rocking of the beta-sheet domain. Consequently, the proton K-pathway becomes sufficiently flexible for internal water molecules to alternately occupy upper and lower parts of the pathway, associated with conserved Thr-359 and Lys-362 residues. The D-pathway helices are found to be relatively rigid, with a highly flexible entrance region involving the subunit I C-terminus, potentially regulating the uptake of protons. Constriction and dilation of hydrophobic channels in RsCcO suggest regulation of the oxygen supply to the binuclear center. This analysis points to coupled conformational changes in CcO and their potential to influence both proton and oxygen access.