Electron Transfer within Protein Complexes

描述（申请人提供）：本项目研究蛋白质间电子转移（ET），目的是了解控制蛋白质ET配偶体之间的基本结构、动力学和能量特征;* 蛋白质ET配偶体之间的界面识别和反应性对接; * 对接配偶体之间ET的实际过程。我们研究了三种蛋白质系统，每种系统都提供了解决这些问题的独特机会：混合金属[Zn，Fe 3 +L]血红蛋白杂合物允许我们研究在“预对接”蛋白质-蛋白质复合物内的ET，穿过晶体学定义的非共价偶联界面;细胞色素c过氧化物酶（CcP）与细胞色素c（Cc）的复合物包括作为原型蛋白的CcP，其具有两个ET活性和连通的氧化还原中心，以及用于结合其ET配偶体的两个不同的表面结构域;细胞色素b5与肌红蛋白（Mb）和血红蛋白（Hb）的生理学上重要的ET复合物代表了一种新的“动态对接”范例，其中存在许多对接构型，但最具反应性的不是最有利于结合的构型。 在上述目标下的一系列广泛的个人目标，我们只注意到几个是我们在未来一段时间内的努力的核心：（一）表征蛋白质波动控制蛋白质间ET的方式，以及它们可以通过耦合到外部介质进行调制的程度。(ii)确定两个CcP位点之间的ET在CcP和Cc之间的ET动力学中的作用。(iii)实施一项计划，通过实验确定偶极力（而不是双极相互作用）控制蛋白质-蛋白质对接的程度。为了实现我们的目标，我们将应用和扩展广泛的动力学，热力学，光谱和理论方法。 新的方法和策略包括，除其他外，在溶胶-凝胶中蛋白质-蛋白质ET的广泛研究。 我们解决的问题和我们开发的策略的应用远远超出了我们研究的ET反应。

DESCRIPTION (provided by applicant): This program in the study of inter-protein electron transfer (ET) aims to understand the fundamental structural, dynamic and energetic features that control, * lnterfacial recognition and reactive docking between protein ET partners; *The actual process of ET between docked partners.We study three protein systems, each offering distinct opportunities to address these issues: mixed-metal [Zn, Fe3+L] hemoglobin hybrids allow us to study ET within a 'predocked' protein-protein complex, across a crystallographically defined, non-covalently coupled interface; the complex of cytochrome c peroxidase (CcP) with cytochrome c (Cc) involves CcP as the archetypical protein which has two ET-active and communicating redox centers, as well as two distinct surface domains for binding its ET partner; the physiologically important ET complexes of cytochrome b5 with myoglobin (Mb) and hemoglobin (Hb) represent a new 'dynamic docking' paradigm in which there are many docked configurations, but the most reactive are not the most favorable for binding. Among a broad array of individual goals subsumed under the above aims, we merely note several that are central to our efforts in the coming period: (i) Characterize the ways in which protein fluctuations control interprotein ET, and the degree to which they can be modulated by coupling to the external medium .(ii) Establish the role of ET between the two CcP sites in the kinetics of ET between CcP and Cc. (iii) Implement a plan to experimentally establish the degree to which dipole forces, rather than monopole interactions, control protein-protein docking. To realize our aims, we shall apply and extend a broad range of kinetic, thermodynamic, spectroscopic, and theoretical methods. New approaches and strategies include, among others, extensive studies of protein-protein ET in sol-gels. The issues we address and the strategies we develop have applications extending far beyond the ET reaction we study.