Structural basis for recognition by an in vitro evolved affibody
- *Department of Biochemistry and Biophysics, Stockholm University, Roslagstullsbacken 15, and †Department of Biotechnology, Royal Institute of Technology, Roslagstullsbacken 21, Albanova University Center, SE-11421 Stockholm, Sweden
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Edited by Adriaan Bax, National Institutes of Health, Bethesda, MD, and approved December 27, 2002 (received for review October 9, 2002)
Abstract
The broad binding repertoire of antibodies has permitted their use in a wide range of applications. However, some uses of antibodies are precluded due to limitations in the efficiency of antibody generation. In vitro evolved binding proteins, selected from combinatorial libraries generated around various alternative structural scaffolds, are promising alternatives to antibodies. We have solved the crystal structure of a complex of an all α-helical in vitro selected binding protein (affibody) bound to protein Z, an IgG Fc-binding domain derived from staphylococcal protein A. The structure of the complex reveals an extended and complementary binding surface with similar properties to protein–antibody interactions. The surface region of protein Z recognized by the affibody is strikingly similar to the one used for IgG1 Fc binding, suggesting that this surface contains potential hot-spots for binding. The implications of the selected affibody binding-mode for its application as a universal binding protein are discussed.
Footnotes
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↵ ‡ To whom correspondence should be addressed. E-mail: par.nordlund{at}dbb.su.se.
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This paper was submitted directly (Track II) to the PNAS office.
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Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID code ).
- Abbreviations:
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SPA, staphylococcal protein A
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- Copyright © 2003, The National Academy of Sciences
