Antibody-protein binding and conformational changes: identifying allosteric signalling pathways to engineer a better
Mohammed M Al Qaraghuli1,2, Karina Kubiak-Ossowska3,4, Valerie A Ferro5
1Department of Chemical and Process Engineering, University of Strathclyde, Glasgow, G1 1XJ, UK. mohammed.al-qaraghuli@strath.ac.uk.
Scientific Reports
|August 15, 2020
Summary
Structural analysis reveals three classes of antibody changes upon antigen binding. Understanding these allosteric movements is crucial for developing more effective therapeutic antibodies.
Area of Science:
- Biochemistry
- Structural Biology
- Immunology
Background:
- Monoclonal antibodies are vital therapeutics, but their development is costly and lengthy.
- Detailed structural analysis beyond the binding site is needed to improve antibody efficacy.
- Protein antigens induce significant antibody structural changes, making them ideal for study.
Purpose of the Study:
- To analyze the structural changes in anti-protein antibodies upon antigen binding.
- To compare antigen-bound and unbound antibody structures.
- To identify distinct classes of binding-induced structural alterations.
Main Methods:
- Structural analysis of 15 anti-protein antibodies.
- Comparison of antigen-bound and unbound antibody forms.
- Identification and classification of binding-induced structural changes.
Main Results:
- Three distinct classes of antibody structural changes were identified.
- Class B1: Significant antigen-binding fragment distortion with constant domain loop changes (allosteric movements).
- Class B2: Constant domain loop changes without overall distortion.
- Class B3: Only local changes within complementarity determining regions.
Conclusions:
- Structural analysis of antibodies is critical for therapeutic development.
- Evaluating allosteric movements is essential for enhancing antibody effector responses.
- Understanding these changes is vital during antibody development from fragments to full antibodies.
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