Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold.
Publication
, Journal Article
Azoitei, ML; Correia, BE; Ban, Y-EA; Carrico, C; Kalyuzhniy, O; Chen, L; Schroeter, A; Huang, P-S; McLellan, JS; Kwong, PD; Baker, D ...
Published in: Science
October 21, 2011
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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Published In
Science
DOI
EISSN
1095-9203
Publication Date
October 21, 2011
Volume
334
Issue
6054
Start / End Page
373 / 376
Location
United States
Related Subject Headings
- Surface Plasmon Resonance
- Protein Interaction Domains and Motifs
- Protein Engineering
- Protein Conformation
- Mutagenesis
- Molecular Sequence Data
- Molecular Mimicry
- Models, Molecular
- HIV Envelope Protein gp120
- HIV Antibodies
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ICMJE
MLA
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Azoitei, M. L., Correia, B. E., Ban, Y.-E., Carrico, C., Kalyuzhniy, O., Chen, L., … Schief, W. R. (2011). Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold. Science, 334(6054), 373–376. https://doi.org/10.1126/science.1209368
Azoitei, Mihai L., Bruno E. Correia, Yih-En Andrew Ban, Chris Carrico, Oleksandr Kalyuzhniy, Lei Chen, Alexandria Schroeter, et al. “Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold.” Science 334, no. 6054 (October 21, 2011): 373–76. https://doi.org/10.1126/science.1209368.
Azoitei ML, Correia BE, Ban Y-EA, Carrico C, Kalyuzhniy O, Chen L, et al. Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold. Science. 2011 Oct 21;334(6054):373–6.
Azoitei, Mihai L., et al. “Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold.” Science, vol. 334, no. 6054, Oct. 2011, pp. 373–76. Pubmed, doi:10.1126/science.1209368.
Azoitei ML, Correia BE, Ban Y-EA, Carrico C, Kalyuzhniy O, Chen L, Schroeter A, Huang P-S, McLellan JS, Kwong PD, Baker D, Strong RK, Schief WR. Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold. Science. 2011 Oct 21;334(6054):373–376.
Published In
Science
DOI
EISSN
1095-9203
Publication Date
October 21, 2011
Volume
334
Issue
6054
Start / End Page
373 / 376
Location
United States
Related Subject Headings
- Surface Plasmon Resonance
- Protein Interaction Domains and Motifs
- Protein Engineering
- Protein Conformation
- Mutagenesis
- Molecular Sequence Data
- Molecular Mimicry
- Models, Molecular
- HIV Envelope Protein gp120
- HIV Antibodies