Publication Date:
2011-10-25
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Azoitei, Mihai L -- Correia, Bruno E -- Ban, Yih-En Andrew -- Carrico, Chris -- Kalyuzhniy, Oleksandr -- Chen, Lei -- Schroeter, Alexandria -- Huang, Po-Ssu -- McLellan, Jason S -- Kwong, Peter D -- Baker, David -- Strong, Roland K -- Schief, William R -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Oct 21;334(6054):373-6. doi: 10.1126/science.1209368.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22021856" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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