Changes at the intersubunit interface of human Hemoglobin A upon effector binding does not result in a compressibility change at the heme pocket.

Gusztav Schay 1,2Laszlo Smeller 1Takashi Yonetani 3Judit Fidy 1,2

1. Semmelweis University, Institute of Biophysics and Radiation Biology, Puskin u. 9. PF 263, Budapest H-1444, Hungary
2. Hungarian Academy of Sciences, Research Group for Membrane Biology (MTAGRMB), Daroczi u 24., Budapest 1113, Hungary
3. University of Pennsylvania (PENN), 3231 Walnut St., Philadelphia 19104, United States

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The mechanism of allostery in Hemoglobin is still not completely understood. Various models have been published in the literature, however the details of the communication pathway are still not completely clear. Recently a new model has been proposed ( Yonetani et al, 2002 J. Biol. Chem. 277, 34508-34520) which relates global tertiary conformational changes to allostery. In this framework, in every subunit tertiary conformational changes occur upon the binding of allosteric effectors, that lead to the observed changes in oxygen binding affinity. We have shown (Fidy et al, 2006 BBA Proteins and Proteomics 1764(3):516-21 ; and Fidy et al, 2006. submitted to J. Biol. Chem.) , that substantial conformational changes occur at the interdimeric interface region of every subunit upon the binding of allosteric effectors. We have extended this study, to assess possible changes at other parts of the protein matrix, and thus gain additional knowledge about the communication pathway. In this study we used a zinc hybrid, and fluorescence line narrowing to assess the compressibility of the matrix around the heme. We have shown, that the high-pressure compressibility of the heme pockets - measured by using high pressure - does not change significantly upon the binding of allosteric effectors. This suggests that changes in oxygen binding are related to the fine tuning of the structural conditions in the heme pocket, which can not be observed when the protein is compressed by pressures higher than 1 kbar.

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Presentation: Poster at COST D30 Final Evaluation Meeting, by Gusztav Schay
See On-line Journal of COST D30 Final Evaluation Meeting

Submitted: 2007-10-03 22:26
Revised:   2009-06-07 00:44
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