Conformational selection and induced fit mechanism underlie specificity in noncovalent interactions with ubiquitin

Proceedings of the National Academy of Sciences of the United States of America - Tập 106 Số 46 - Trang 19346-19351 - 2009
Tomasz Włodarski1,2, Bojan Žagrović3,2
1Laboratory of Bioinformatics and Bioengineering, Interdisciplinary Centre for Mathematical and Computational Modeling, University of Warsaw, Zwirki i Wigury 93, 02-089, Warsaw, Poland;
2Laboratory of Computational Biophysics, Mediterranean Institute for Life Sciences, Mestrovicevo setaliste b.b., 21000 Split, Croatia; and
3Department of Physics, University of Split, 2100 Split, Croatia

Tóm tắt

Noncovalent binding interactions between proteins are the central physicochemical phenomenon underlying biological signaling and functional control on the molecular level. Here, we perform an extensive structural analysis of a large set of bound and unbound ubiquitin conformers and study the level of residual induced fit after conformational selection in the binding process. We show that the region surrounding the binding site in ubiquitin undergoes conformational changes that are significantly more pronounced compared with the whole molecule on average. We demonstrate that these induced-fit structural adjustments are comparable in magnitude to conformational selection. Our final model of ubiquitin binding blends conformational selection with the subsequent induced fit and provides a quantitative measure of their respective contributions.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 106 Số 46

19346-19351

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