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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Song, Hang Kaczynska, Anna Felsovalyi, Klara Yang, Zhongyu Brasch, Julia Harrison, Oliver J. Edmond, Darwin Bahna, Fabiana Katsamba, Phinikoula S. Jin, Xiangshu Hubbell, Wayne L. Vendome, Jeremie Honig, Barry Ahlsen, Goran Shapiro, Lawrence |
| Description | Author Affiliation: Vendome J ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Department of Systems Biology, Howard Hughes Medical Institute, Columbia University, New York, NY 10032); Felsovalyi K ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Department of Systems Biology, Howard Hughes Medical Institute, Columbia University, New York, NY 10032); Song H ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Department of Systems Biology, Howard Hughes Medical Institute, Columbia University, New York, NY 10032); Yang Z ( Jules Stein Eye Institute and.); Jin X ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Howard Hughes Medical Institute, Columbia University, New York, NY 10032); Brasch J ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Department of Systems Biology.); Harrison OJ ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Department of Systems Biology, Howard Hughes Medical Institute, Columbia University, New York, NY 10032); Ahlsen G ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Department of Systems Biology, Howard Hughes Medical Institute, Columbia University, New York, NY 10032); Bahna F ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Department of Systems Biology, Howard Hughes Medical Institute, Columbia University, New York, NY 10032); Kaczynska A ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Department of Systems Biology.); Katsamba PS ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Department of Systems Biology, Howard Hughes Medical Institute, Columbia University, New York, NY 10032); Edmond D ( Department of Physics, University of Washington, Seattle, WA 98195); Hubbell WL ( Jules Stein Eye Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 hubbellw@jsei.ucla.edu lss8@columbia.edu bh6@columbia.edu.); Shapiro L ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Department of Systems Biology, hubbellw@jsei.ucla.edu lss8@columbia.edu bh6@columbia.edu.); Honig B ( Department of Biochemistry and Molecular Biophysics, Center for Computational Biology and Bioinformatics, Department of Systems Biology, Howard Hughes Medical Institute, Columbia University, New York, NY 10032); |
| Abstract | Type I cadherin cell-adhesion proteins are similar in sequence and structure and yet are different enough to mediate highly specific cell-cell recognition phenomena. It has previously been shown that small differences in the homophilic and heterophilic binding affinities of different type I family members can account for the differential cell-sorting behavior. Here we use a combination of X-ray crystallography, analytical ultracentrifugation, surface plasmon resonance and double electron-electron resonance (DEER) electron paramagnetic resonance spectroscopy to identify the molecular determinants of type I cadherin dimerization affinities. Small changes in sequence are found to produce subtle structural and dynamical changes that impact relative affinities, in part via electrostatic and hydrophobic interactions, and in part through entropic effects because of increased conformational heterogeneity in the bound states as revealed by DEER distance mapping in the dimers. These findings highlight the remarkable ability of evolution to exploit a wide range of molecular properties to produce closely related members of the same protein family that have affinity differences finely tuned to mediate their biological roles. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 40 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cadherins Chemistry Protein Multimerization Protein Structure, Secondary Protein Structure, Tertiary Amino Acid Sequence Animals Binding, Competitive Genetics Metabolism Crystallography, X-Ray Electron Spin Resonance Spectroscopy HEK293 Cells Hydrophobic And Hydrophilic Interactions Kinetics Mice Models, Molecular Molecular Sequence Data Mutation Protein Binding Sequence Homology, Amino Acid Static Electricity Xenopus Xenopus Proteins Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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