Epitopes described in "Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold."

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
Article Title:Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold.
Reference Detail
Reference ID:1025015
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.
Affiliations:Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Reference Type:Literature
PubMed ID:22021856
Journal Volume:334
Article Pages:373-6
Journal ISSN:1095-9203
Article Chemical List:Antibodies, Monoclonal;Antibodies, Neutralizing;Antigens, CD4;Epitopes;HIV Antibodies;HIV Envelope Protein gp120
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
Curation Last Updated:2014-10-03 22:46:53