Science (American Association for the Advancement of Science), 2011-10, Vol.334 (6054), p.373-376
2011
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Details
- Autor(en) / Beteiligte
- Titel
- Computation-Guided Backbone Grafting of a Discontinuous Motif onto a Protein Scaffold
- Ist Teil von
- Science (American Association for the Advancement of Science), 2011-10, Vol.334 (6054), p.373-376
- Ort / Verlag
- Washington, DC: American Association for the Advancement of Science
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1209368Titel-ID: cdi_proquest_miscellaneous_900636914
- Format
- –
- Schlagworte
- Algorithms, Amino Acid Motifs, Amino Acid Sequence, Analytical, structural and metabolic biochemistry, Antibodies, Antibodies, Monoclonal - chemistry, Antibodies, Monoclonal - immunology, Antibodies, Monoclonal - metabolism, Antibodies, Neutralizing - chemistry, Antibodies, Neutralizing - immunology, Antibodies, Neutralizing - metabolism, Antibody Affinity, Antibody Specificity, Antigens, Biological and medical sciences, CD4 Antigens - metabolism, Computational Biology, Computer Simulation, Crystallography, X-Ray, Enzymes, Epitopes, Epitopes - immunology, Fundamental and applied biological sciences. Psychology, HIV, HIV Antibodies - chemistry, HIV Antibodies - immunology, HIV Antibodies - metabolism, HIV Envelope Protein gp120 - chemistry, HIV Envelope Protein gp120 - immunology, HIV Envelope Protein gp120 - metabolism, Human immunodeficiency virus, Libraries, Models, Molecular, Molecular and cellular biology, Molecular Mimicry, Molecular Sequence Data, Mutagenesis, Mutagenicity tests, Odes, Protein Conformation, Protein Engineering, Protein Interaction Domains and Motifs, Proteins, Scaffolds, Spine, Surface Plasmon Resonance, Tissue grafting