Visualizing breathing motion of internal cavities in concert with ligand migration in myoglobin
Visualizing breathing motion of internal cavities in concert with ligand migration in myoglobin
复制标题
DOI：
10.1073/pnas.0807774106
复制
发表时间：
2009-02-24
影响因子：
11.1
通讯作者：
Adachi, Shin-ichi
中科院分区：
文献类型：
--
作者：
Tomita, Ayana;Sato, Tokushi;Adachi, Shin-ichi
蛋白质含有许多相对较小体积的空腔。虽然这些包装缺陷与蛋白质的热力学不稳定性有关，但这些空洞也在控制蛋白质功能方面发挥着特殊的作用，如配体迁移和结合。这个问题已经在一种众所周知的蛋白质--肌红蛋白(Mb)中得到了广泛的研究。MB可逆地结合埋在蛋白质基质中的血红素位置上的气体配体，并具有几个内部空腔，配体分子可以驻留在其中。关于配体如何在内腔之间找到其迁移路径，仍然是一个悬而未决的问题。在这里，我们报告了Mb在配体迁移过程中内部空穴的动态和顺序结构变形。我们的方法，用脉冲激光在低温下连续照射天然的一氧化碳Mb晶体，揭示了CO分子迁移到每个空腔导致空腔周围氨基酸残基的结构变化，从而导致空腔的膨胀和呼吸运动。配体和空穴的顺序运动表明了诱导匹配引起的配体迁移通道的自开放机制，这一机制得到了Delaunay网格方法计算几何分析的进一步支持。这一结果表明，作为蛋白质基质中配体迁移的一般机制，内腔的呼吸运动起着至关重要的作用。
Proteins harbor a number of cavities of relatively small volume. Although these packing defects are associated with the thermodynamic instability of the proteins, the cavities also play specific roles in controlling protein functions, e. g., ligand migration and binding. This issue has been extensively studied in a well-known protein, myoglobin (Mb). Mb reversibly binds gas ligands at the heme site buried in the protein matrix and possesses several internal cavities in which ligand molecules can reside. It is still an open question as to how a ligand finds its migration pathways between the internal cavities. Here, we report on the dynamic and sequential structural deformation of internal cavities during the ligand migration process in Mb. Our method, the continuous illumination of native carbonmonoxy Mb crystals with pulsed laser at cryogenic temperatures, has revealed that the migration of the CO molecule into each cavity induces structural changes of the amino acid residues around the cavity, which results in the expansion of the cavity with a breathing motion. The sequential motion of the ligand and the cavity suggests a self-opening mechanism of the ligand migration channel arising by induced fit, which is further supported by computational geometry analysis by the Delaunay tessellation method. This result suggests a crucial role of the breathing motion of internal cavities as a general mechanism of ligand migration in a protein matrix.