ISTCT CNRS UNICAEN CEA Normandie Univ., CERVOxy team, centre Cyceron, 14000, Caen, France.
Laboratoire de Biochimie Théorique, CNRS UPR9080, Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005, Paris, France.
Sci Rep. 2017 May 12;7(1):1858. doi: 10.1038/s41598-017-02097-1.
Investigating the effect of pressure sheds light on the dynamics and plasticity of proteins, intrinsically correlated to functional efficiency. Here we detail the structural response to pressure of neuroglobin (Ngb), a hexacoordinate globin likely to be involved in neuroprotection. In murine Ngb, reversible coordination is achieved by repositioning the heme more deeply into a large internal cavity, the "heme sliding mechanism". Combining high pressure crystallography and coarse-grain simulations on wild type Ngb as well as two mutants, one (V101F) with unaffected and another (F106W) with decreased affinity for CO, we show that Ngb hinges around a rigid mechanical nucleus of five hydrophobic residues (V68, I72, V109, L113, Y137) during its conformational transition induced by gaseous ligand, that the intrinsic flexibility of the F-G loop appears essential to drive the heme sliding mechanism, and that residue Val 101 may act as a sensor of the interaction disruption between the heme and the distal histidine.
研究压力对蛋白质动力学和可塑的影响，这与功能效率密切相关。在此，我们详细介绍神经球蛋白（Ngb）对压力的结构响应，Ngb 是一种六配位球蛋白，可能与神经保护有关。在鼠类 Ngb 中，通过将血红素更深地重新定位到一个大的内部腔中，实现了可逆配位，这个过程被称为“血红素滑动机制”。我们结合高压晶体学和对野生型 Ngb 以及两种突变体（V101F 和 F106W）的粗粒度模拟，这两种突变体的一氧化碳亲和力没有受到影响和降低，结果表明，在气态配体诱导的构象转变过程中，Ngb 围绕着一个由五个疏水性残基（V68、I72、V109、L113、Y137）组成的刚性机械核，F-G 环的固有灵活性对于驱动血红素滑动机制至关重要，并且残基 Val 101 可能充当血红素与远端组氨酸之间相互作用中断的传感器。
