期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2106690118|1of9
关键词
IDP; single-molecule; protein dynamics; fuzzy complex; molecular simulation
资金
- Israel Science Foundation [1549/15]
- Benoziyo Fund for the Advancement of Science
- Carolito Foundation
- Leir Charitable Foundation
- Koshland family
- NSF [MCB-2015030]
Intrinsically disordered proteins form dynamic complexes with their ligands, with motions hidden in classical binding kinetics. By directly measuring dynamics in a highly mobile, high-affinity complex, researchers found that the energy landscape of the complex is rugged with small barriers reconciling specificity, high affinity, and extreme disorder. Single-molecule experiments and molecular simulations provide high resolution in space and time for resolving these motions.
Intrinsically disordered proteins often form dynamic complexes with their ligands. Yet, the speed and amplitude of these motions are hidden in classical binding kinetics. Here, we directly measure the dynamics in an exceptionally mobile, high-affinity complex. We show that the disordered tail of the cell adhesion protein E-cadherin dynamically samples a large surface area of the protooncogene beta-catenin. Single-molecule experiments and molecular simulations resolve these motions with high resolution in space and time. Contacts break and form within hundreds of microseconds without a dissociation of the complex. The energy landscape of this complex is rugged with many small barriers (3 to 4 kBT) and reconciles specificity, high affinity, and extreme disorder. A few persistent contacts provide specificity, whereas unspecific interactions boost affinity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据