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Updated: May 25, 2026
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Isolation of Labile Multi-protein Complexes by in vivo Controlled Cellular Cross-Linking and Immuno-magnetic Affinity Chromatography
Published on: March 9, 2010
Structures of adnectin/protein complexes reveal an expanded binding footprint
Vidhyashankar Ramamurthy1, Stanley R Krystek, Alexander Bush
1Bristol-Myers Squibb Research & Development, Princeton, NJ 08543-4000, USA.
Structure (London, England : 1993)
|February 14, 2012
Summary
Adnectins, novel biologics from fibronectin, bind unique therapeutic targets like EGFR and IL-23. Their distinct binding sites, including non-loop regions, offer new therapeutic possibilities beyond antibodies.
Area of Science:
- Biochemistry
- Molecular Biology
- Protein Engineering
Background:
- Adnectins are engineered protein binders derived from human fibronectin's tenth type III domain (¹⁰Fn3).
- They are designed to target specific molecules, analogous to antibody complementarity determining regions.
- The immunoglobulin superfamily includes fibronectin type III domains.
Purpose of the Study:
- To elucidate the structural basis of Adnectin binding to therapeutic targets.
- To compare Adnectin binding epitopes with those of monoclonal antibodies.
- To investigate the role of non-loop regions in Adnectin-target interactions.
Main Methods:
- Crystal structure determination of Adnectin-EGFR and Adnectin-IL-23 complexes.
- Molecular modeling to analyze binding site accessibility and interactions.
- Alanine-scanning mutagenesis to validate binding contributions.
Main Results:
- Adnectins bind distinct epitopes on EGFR and IL-23 compared to monoclonal antibodies.
- Some Adnectin epitopes are inaccessible to antibodies due to size and shape constraints.
- Interactions involving Adnectin N-terminus and β strands contribute to binding affinity and footprint.
Conclusions:
- Adnectins offer a versatile platform for developing targeted biologics with novel binding mechanisms.
- Non-loop residues significantly expand the binding capabilities of Adnectins.
- Adnectins present a promising alternative to antibodies for targeting specific epitopes.
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