Heterogeneous and rate-dependent streptavidin-biotin unbinding revealed by high-speed force spectroscopy and molecular dynamics simulations
Heterogeneous and rate-dependent streptavidin-biotin unbinding revealed by high-speed force spectroscopy and molecular dynamics simulations
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高速力谱和分子动力学模拟揭示了异质且速率依赖性链霉亲和素-生物素解结合
DOI：
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
S. Scheuring
中科院分区：
文献类型：
--
作者：
F. Rico;A. Russek;L. González;H. Grubmüller;S. Scheuring
受体-配体相互作用对于生物学功能是必不可少的，并且它们的结合强度通常根据基于分子互补性的静态锁和钥匙模型来解释。然而，完整的解结合途径的详细信息通常是缺乏的，部分原因是原子结构的静态性质和整体生物物理方法固有的系综平均。在这里，我们结合联合收割机分子动力学和高速力光谱的链霉亲和素-生物素复合物，以确定结合强度和最宽的动态范围内的解结合途径。实验和模拟结果表明，在重叠的速度非常一致，并提供了证据的解绑机制。在解结合过程中，生物素穿过多个能量屏障并访问远离结合口袋的各种中间状态，而链霉亲和素经历瞬时诱导的拟合，所有这些都随加载速率而变化。这种多状态过程减慢了向未结合状态的转变并有利于重新结合，从而解释了复合物的长寿命。我们提供了一个原子的，动态的解绑过程中的图片，这表明锁和钥匙机制可能需要修改的锁，可能是相关的其他受体-配体键的许多路线。
Receptor-ligand interactions are essential for biological function and their binding strength is commonly explained in terms of static lock-and-key models based on molecular complementarity. However, detailed information of the full unbinding pathway is commonly lacking due, in part, to the static nature of atomic structures and ensemble averaging inherent to bulk biophysics approaches. Here we combine molecular dynamics and high-speed force spectroscopy on the streptavidin-biotin complex to determine the binding strength and unbinding pathways over the widest dynamic range. Experiment and simulation show excellent agreement at overlapping velocities and provided evidence of the unbinding mechanisms. During unbinding, biotin crosses multiple energy barriers and visits various intermediate states far from the binding pocket while streptavidin undergoes transient induced fits, all varying with loading rate. This multistate process slows down the transition to the unbound state and favors rebinding, thus explaining the long lifetime of the complex. We provide an atomistic, dynamic picture of the unbinding process, suggesting that the lock-and-key mechanism may need revision in terms of many routes to the lock that might be relevant for other receptor-ligand bonds.
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影响因子：
16.6
作者：
Bullerjahn, Jakob T.;Sturm, Sebastian;Kroy, Klaus
通讯作者：
Kroy, Klaus
影响因子：
3.4
作者：
D. Tees;Richard E. Waugh;Daniel A. Hammer
通讯作者：
D. Tees;Richard E. Waugh;Daniel A. Hammer
影响因子：
3.4
作者：
Izrailev, S;Stepaniants, S;Schulten, K
通讯作者：
Schulten, K
DOI：
10.1073/pnas.96.15.8384
发表时间：
1999-07-20
影响因子：
11.1
作者：
Freitag, S;Chu, V;Stayton, PS
通讯作者：
Stayton, PS
配体-受体键的协同粘附。
影响因子：
3.8
作者：
Zhang,Xiaohui;Moy,VincentT
通讯作者：
Moy,VincentT