Abstract
Antibodies are well known for their high specificity that has enabled them to be of significant use in both therapeutic and diagnostic applications. Antibodies can recognize different antigens, including proteins, carbohydrates, peptides, nucleic acids, lipids, and small molecular weight haptens that are abundantly available as hormones, pharmaceuticals, and pesticides. Here we focus on a structural analysis of hapten-antibody couples and identify potential structural movements originating from the hapten binding by comparison with unbound antibody, utilizing 40 crystal structures from the Protein Data Bank. Our analysis reveals three binding surface trends; S1 where a pocket forms to accommodate the hapten, S2 where a pocket is removed when the hapten binds, and S3 where no pockets changes are found. S1 and S2 are expected for induced-fit binding, whereas S3 indicates that a pre-existing population of optimal binding antibody conformation exists. The structural analysis reveals four classifications of structural reorganization, some of which correlate to S2 but not to the other binding surface changes. These observations demonstrate the complexity of the antibody-antigen interaction, where structural changes can be restricted to the binding sites, or extend through the constant domains to propagate structural changes. This highlights the importance of structural analysis to ensure successful and compatible transformation of small antibody fragments at the early discovery stage into full antibodies during the subsequent development stages, where long-range structural changes are required for an Fc effector response.
Highlights
The immune system represents a major defensive mechanism that protects vertebrates against pathogen invasion
In this paper we have extended our analysis of Fab structural changes induced by antigen binding from proteins (Al Qaraghuli et al, 2020) to haptens
Crystal structures of anti-hapten antibodies were retrieved from the Protein Data Bank (PDB), and comprehensive analyses were conducted to examine their binding sites and the structural changes caused by antigen binding
Summary
The immune system represents a major defensive mechanism that protects vertebrates against pathogen invasion Within this system, lymphocytes synthesize cell surface receptors or secrete glycoproteins, known as antibodies, which bind to foreign molecules (Alberts et al, 2002). An antibody of class IgG is normally composed of two light and two heavy chains linked together by disulphide bonds. These heavy and light chains create two identical antigen-binding fragments (Fabs), each contain the first two domains of the heavy (VH and CH1) and light (VL and CL) chains, and one crystallizable region fragment (Fc), each comprising CH2 and CH3 domains (Porter, 1959; Ryle and Porter, 1959). Each variable (VH and VL) domain contains three CDRs, and the resulting six CDRs collectively represent the antigen binding sites
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
