Journal
SCIENCE
Volume 334, Issue 6054, Pages 373-376Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1209368
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Funding
- International AIDS Vaccine Initiative Neutralizing Antibody Consortium
- Bill and Melinda Gates Foundation Consortium for AIDS Vaccine Discovery
- Portuguese Fundacao para a Ciencia e a Tecnologia [SFRH/774 BD/32958/2006]
- PDB [3RPT, 3RU8]
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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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