Structural Assembly of Multidomain Proteins and Protein Complexes Guided by the Overall Rotational Diffusion Tensor
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- 作者：Yaroslav Ryabov ; David Fushman
- 刊名：Journal of the American Chemical Society
- 出版年：2007
- 出版时间：June 27, 2007
- 年：2007
- 卷：129
- 期：25
- 页码：7894 - 7902
- 全文大小：639K
- 年卷期：v.129,no.25(June 27, 2007)
- ISSN：1520-5126
文摘
We present a simple and robust approach that uses the overall rotational diffusion tensor as astructural constraint for domain positioning in multidomain proteins and protein-protein complexes. Thismethod offers the possibility to use NMR relaxation data for detailed structure characterization of suchsystems provided the structures of individual domains are available. The proposed approach extends theconcept of using long-range information contained in the overall rotational diffusion tensor. In contrast tothe existing approaches, we use both the principal axes and principal values of protein's rotational diffusiontensor to determine not only the orientation but also the relative positioning of the individual domains in aprotein. This is achieved by finding the domain arrangement in a molecule that provides the best possibleagreement with all components of the overall rotational diffusion tensor derived from experimental data.The accuracy of the proposed approach is demonstrated for two protein systems with known domainarrangement and parameters of the overall tumbling: the HIV-1 protease homodimer and Maltose BindingProtein. The accuracy of the method and its sensitivity to domain positioning are also tested using computer-generated data for three protein complexes, for which the experimental diffusion tensors are not available.In addition, the proposed method is applied here to determine, for the first time, the structure of both openand closed conformations of a Lys48-linked diubiquitin chain, where domain motions render impossibleaccurate structure determination by other methods. The proposed method opens new avenues for improvingstructure characterization of proteins in solution.