Project 1: Biophysics of the IkBa/NFkB Interaction

拟议的工作的总体目标是提供一个定量的生物物理描述的蛋白质折叠和结合动力学和热力学的kB家族的成员，因为他们与NF κ B家族的成员相互作用。与Wolynes项目的整合将使理论和实验相关联，以更深入地了解蛋白质结构如何决定其生物物理特性。与戴森项目的整合将跨越时间尺度的界限，从NMR时间尺度动力学到H/D交换和smFRET探测的更长时间尺度。与霍夫曼和高希项目的整合将提供生物物理特性和功能之间的联系。该项目的重点是iKBa AR 5-AR 6-C-末端EST包含区域的内在紊乱及其在建立NF κ B信号传导的功能控制中的作用。

The overall goal of the proposed work is to provide a quantitative biophysical description of the protein folding and binding kinetics and thermodynamics of members of the kB family as they interact with members of the NFKB family. Integration with the Wolynes project will correlate theory and experiment to develop a deeper understanding of how the protein structure determines its biophysical properties. Integration with the Dyson project will cross the time-scale boundaries from NMR time scale dynamics to longer time scales probed by H/D exchange and smFRET. Integration with the Hoffmann and Ghosh projects will provide a link between biophysical properties and function. A focus of the project is the intrinsic disorder of iKBa AR5-AR6-C-terminal EST-containing region and its role in establishing functional control of NFKB signaling.