实时观察配体诱导的PDZ结构域的变构转变
Real-time observation of ligand-induced allosteric transitions in a PDZ domain
摘要：
虽然变构对于蛋白质调节是至关重要的，但是在一个位点处配体结合（不结合）的潜在动力学过程、导致蛋白质结构的时间演变以及在远程位点处结合亲和力的变化还没有被很好地理解。在这里，配体诱导的构象转变，在一个广泛研究的模型系统的变构，PDZ 2域，进行了研究瞬态红外光谱伴随分子动力学模拟。为此，偶氮苯衍生的光开关以其对PDZ 2结构域的结合亲和力在切换时改变的方式连接至肽配体，从而引发PDZ 2结构域蛋白中的变构转变。蛋白质的随后响应，覆盖从$\sim$ 1~ns到$\sim$ 10~ $μ$ s的40年时间，可以通过重塑其崎岖的自由能景观来合理化，在少数结构明确定义的状态的群体中具有非常微妙的变化。有人提出，结构和动态驱动的变构，通常被讨论为变构通信的限制方案，实际上是齐头并进的，允许蛋白质适应其自由能景观传入信号。
英文摘要：
While allostery is of paramount importance for protein regulation, the underlying dynamical process of ligand (un)binding at one site, resulting time evolution of the protein structure, and change of the binding affinity at a remote site is not well understood. Here the ligand-induced conformational transition in a widely studied model system of allostery, the PDZ2 domain, is investigated by transient infrared spectroscopy accompanied by molecular dynamics simulations. To this end, an azobenzene derived photoswitch is linked to a peptide ligand in a way that its binding affinity to the PDZ2 domain changes upon switching, thus initiating an allosteric transition in the PDZ2 domain protein. The subsequent response of the protein, covering four decades of time ranging from $\sim$1~ns to $\sim$10~$μ$s, can be rationalize by a remodelling of its rugged free energy landscape, with ver subtle shifts in the populations of a small number of structurally well defined states. It is proposed that structurally and dynamically driven allostery, often discussed as limiting scenarios of allosteric communication, actually go hand-in-hand, allowing the protein to adapt its free energy landscape to incoming signals.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
