Molecular basis of a million-fold affinity maturation process in a protein-protein interaction
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Authors
Bonsor, Daniel A.Postel, Sandra
Pierce, Brian G.
Wang, Ningyan
Zhu, Penny
Buonpane, Rebecca A.
Weng, Zhiping
Kranz, David M.
Sundberg, Eric J.
UMass Chan Affiliations
Program in Bioinformatics and Integrative BiologyDepartment of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2011-08-12Keywords
Bacterial ProteinsCrystallography, X-Ray
Models, Molecular
Mutagenesis
Mutant Proteins
Protein Binding
Protein Engineering
*Protein Interaction Mapping
Protein Structure, Quaternary
Receptors, Antigen, T-Cell
Amino Acids, Peptides, and Proteins
Bioinformatics
Computational Biology
Molecular Biology
Systems Biology
Metadata
Show full item recordAbstract
Protein engineering is becoming increasingly important for pharmaceutical applications where controlling the specificity and affinity of engineered proteins is required to create targeted protein therapeutics. Affinity increases of several thousand-fold are now routine for a variety of protein engineering approaches, and the structural and energetic bases of affinity maturation have been investigated in a number of such cases. Previously, a 3-million-fold affinity maturation process was achieved in a protein-protein interaction composed of a variant T-cell receptor fragment and a bacterial superantigen. Here, we present the molecular basis of this affinity increase. Using X-ray crystallography, shotgun reversion/replacement scanning mutagenesis, and computational analysis, we describe, in molecular detail, a process by which extrainterfacial regions of a protein complex can be rationally manipulated to significantly improve protein engineering outcomes.Source
J Mol Biol. 2011 Aug 12;411(2):321-8. doi: 10.1016/j.jmb.2011.06.009. Link to article on publisher's site
DOI
10.1016/j.jmb.2011.06.009Permanent Link to this Item
http://hdl.handle.net/20.500.14038/25882PubMed ID
21689661Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.jmb.2011.06.009
Scopus Count
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