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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Heu, Woosung Lee, Seung-goo Hong, Seungpyo Kim, Hyun Jung Kim, Dongsup Ha, Jae-seok Lee, Sang-chul Lee, Joong-jae Park, Keunwan Cheong, Hae-kap Jeon, Young Ho Kim, Yu Jung Kim, Hak-sung Han, Jieun |
| Description | Author Affiliation: Lee SC ( Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Korea.); |
| Abstract | Repeat proteins have recently been of great interest as potential alternatives to immunoglobulin antibodies due to their unique structural and biophysical features. We here present the development of a binding scaffold based on variable lymphocyte receptors, which are nonimmunoglobulin antibodies composed of Leucine-rich repeat modules in jawless vertebrates, by module engineering. A template scaffold was first constructed by joining consensus repeat modules between the N- and C-capping motifs of variable lymphocyte receptors. The N-terminal domain of the template scaffold was redesigned based on the internalin-B cap by analyzing the modular similarity between the respective repeat units using a computational approach. The newly designed scaffold, termed 'Repebody,' showed a high level of soluble expression in bacteria, displaying high thermodynamic and pH stabilities. Ease of molecular engineering was shown by designing repebodies specific for myeloid differentiation protein-2 and hen egg lysozyme, respectively, by a rational approach. The crystal structures of designed repebodies were determined to elucidate the structural features and interaction interfaces. We demonstrate general applicability of the scaffold by selecting repebodies with different binding affinities for interleukin-6 using phage display. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 9 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Peptide Fragments Chemistry Protein Engineering Receptors, Immunologic Amino Acid Sequence Animals Circular Dichroism Consensus Sequence Crystallography, X-Ray Hagfishes Metabolism Hydrogen-Ion Concentration Lampreys Models, Molecular Molecular Sequence Data Chemical Synthesis Peptide Library Protein Binding Protein Conformation Protein Stability Recombinant Fusion Proteins Substrate Specificity Temperature Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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