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| Article Authors: | Mihai L Azoitei; Bruno E Correia; Yih-En Andrew Ban; Chris Carrico; Oleksandr Kalyuzhniy; Lei Chen; Alexandria Schroeter; Po-Ssu Huang; Jason S McLellan; Peter D Kwong; David Baker; Roland K Strong; William R Schief |
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| Article Title: | Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold. |
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| Reference ID: | 1025015 |
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| Abstract: | The manipulation of protein backbone structure to control interaction and function is a challenge for protein engineering. We integrated computational design with experimental selection for grafting the backbone and side chains of a two-segment HIV gp120 epitope, targeted by the cross-neutralizing antibody b12, onto an unrelated scaffold protein. The final scaffolds bound b12 with high specificity and with affinity similar to that of gp120, and crystallographic analysis of a scaffold bound to b12 revealed high structural mimicry of the gp120-b12 complex structure. The method can be generalized to design other functional proteins through backbone grafting. |
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| Affiliations: | Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. |
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| Date: | 2011 |
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| Reference Type: | Literature |
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| PubMed ID: | 22021856 |
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| Journal: | Science |
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| Journal Volume: | 334 |
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| Article Pages: | 373-6 |
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| Journal ISSN: | 1095-9203 |
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| Article Chemical List: | Antibodies, Monoclonal;Antibodies, Neutralizing;Antigens, CD4;Epitopes;HIV Antibodies;HIV Envelope Protein gp120 |
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| Article MeSH List: | Algorithms; Amino Acid Motifs; Amino Acid Sequence; Antibodies, Monoclonal(chemistry; immunology; metabolism); Antibodies, Neutralizing(chemistry; immunology; metabolism); Antibody Affinity; Antibody Specificity; Antigens, CD4(metabolism); Computational Biology; Computer Simulation; Crystallography, X-Ray; Epitopes(immunology); HIV Antibodies(chemistry; immunology; metabolism); HIV Envelope Protein gp120(chemistry; immunology; metabolism); Models, Molecular; Molecular Mimicry; Molecular Sequence Data; Mutagenesis; Protein Conformation; Protein Engineering; Protein Interaction Domains and Motifs; Surface Plasmon Resonance |
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| Curation Last Updated: | 2013-05-28 22:46:37 |
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