Minority Supplement: Electron Transfer within Protein Complexes

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date8/9/0512/31/08

Funding

  • National Heart, Lung, and Blood Institute (5 R01 HL063203-09)

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