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An affibody in comp...
An affibody in complex with a target protein: Structure and coupled folding.
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- Wahlberg, Elisabet (författare)
- KTH,Bioteknologi
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- Lendel, Christofer (författare)
- KTH,Bioteknologi
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- Helgstrand, Magnus (författare)
- KTH,Bioteknologi
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- Allard, Peter (författare)
- KTH,Bioteknologi
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- Dincbas-Renqvist, Vildan (författare)
- KTH,Bioteknologi
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Hedqvist, Anders (författare)
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- Berglund, Helena (författare)
- KTH,Bioteknologi
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- Nygren, Per-Åke (författare)
- KTH,Bioteknologi
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- Härd, Torleif (författare)
- KTH,Bioteknologi
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(creator_code:org_t)
- 2003-02-19
- 2003
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 100:6, s. 3185-3190
- Relaterad länk:
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http://www.pnas.org/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Combinatorial protein engineering provides powerful means for functional selection of novel binding proteins. One class of engineered binding proteins, denoted affibodies, is based on the three-helix scaffold of the Z domain derived from staphylococcal protein A. The Z(SPA-1) affibody has been selected from a phage-displayed library as a binder to protein A. Z(SPA-1) also binds with micromolar affinity to its own ancestor, the Z domain. We have characterized the Z(SPA-1) affibody in its uncomplexed state and determined the solution structure of a Z:Z(SPA-1) protein-protein complex. Uncomplexed Z(SPA-1) behaves as an aggregation-prone molten globule, but folding occurs on binding, and the original (Z) three-helix bundle scaffold is fully formed in the complex. The structural basis for selection and strong binding is a large interaction interface with tight steric and polar/nonpolar complementarity that directly involves 10 of 13 mutated amino acid residues on Z(SPA-1). We also note similarities in how the surface of the Z domain responds by induced fit to binding of Z(SPA-1) and Ig Fc, respectively, suggesting that the Z(SPA-1) affibody is capable of mimicking the morphology of the natural binding partner for the Z domain.
Ämnesord
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Annan industriell bioteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Other Industrial Biotechnology (hsv//eng)
Nyckelord
- protein engineering
- protein-protein interactions
- molecular recognition
- NMR spectroscopy
- induced fit
- Structural biochemistry
- Strukturbiokemi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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