The immunoglobulin A isotype of the Arabian camel () preserves the dualistic structure of unconventional single-domain and canonical heavy chains.

Introduction: The evolution of adaptive immunity in resulted in the concurrent expression of classic heterotetrameric and unconventional homodimeric heavy chain-only IgG antibodies. Heavy chain-only IgG bears a single variable domain and lacks the constant heavy (C) γ1 domain required for pairing with the light chain. It has not been reported whether this distinctive feature of IgG is also observed in the IgA isotype.

Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines.

Antibodies and other new antibody-like formats have emerged as one of the most rapidly growing classes of biotherapeutic proteins. Understanding the structural features that drive antibody function and, consequently, their molecular recognition is critical for engineering antibodies. Here, we present the structural architecture of conventional IgG antibodies alongside other formats.

Corrigendum: Comparing Antibody Interfaces to Inform Rational Design of New Antibody Formats.

[This corrects the article DOI: 10.3389/fmolb.2022.

Comparing Antibody Interfaces to Inform Rational Design of New Antibody Formats.

As the current biotherapeutic market is dominated by antibodies, the design of different antibody formats, like bispecific antibodies and other new formats, represent a key component in advancing antibody therapy. When designing new formats, a targeted modulation of pairing preferences is key. Several existing approaches are successful, but expanding the repertoire of design possibilities would be desirable.

CDR loop interactions can determine heavy and light chain pairing preferences in bispecific antibodies.

As the current biotherapeutic market is dominated by antibodies, the design of different antibody formats, like bispecific antibodies, is critical to the advancement of the field. In contrast to monovalent antibodies, which consist of two identical antigen-binding sites, bispecific antibodies can target two different epitopes by containing two different antigen-binding sites. Thus, the rise of new formats as successful therapeutics has reignited the interest in advancing and facilitating the efficient production of bispecific antibodies.

Germline-Dependent Antibody Paratope States and Pairing Specific V-V Interface Dynamics.

Antibodies have emerged as one of the fastest growing classes of biotherapeutic proteins. To improve the rational design of antibodies, we investigate the conformational diversity of 16 different germline combinations, which are composed of 4 different kappa light chains paired with 4 different heavy chains. In this study, we systematically show that different heavy and light chain pairings strongly influence the paratope, interdomain interaction patterns and the relative V-V interface orientations.

Mutation of Framework Residue H71 Results in Different Antibody Paratope States in Solution.

Characterizing and understanding the antibody binding interface have become a pre-requisite for rational antibody design and engineering. The antigen-binding site is formed by six hypervariable loops, known as the complementarity determining regions (CDRs) and by the relative interdomain orientation (V-V). Antibody CDR loops with a certain sequence have been thought to be limited to a single static canonical conformation determining their binding properties.

Surprisingly Fast Interface and Elbow Angle Dynamics of Antigen-Binding Fragments.

Fab consist of a heavy and light chain and can be subdivided into a variable (V and V ) and a constant region (C 1 and C ). The variable region contains the complementarity-determining region (CDR), which is formed by six hypervariable loops, shaping the antigen binding site, the paratope. Apart from the CDR loops, both the elbow angle and the relative interdomain orientations of the V -V and the C 1-C domains influence the shape of the paratope.

Antibodies exhibit multiple paratope states influencing V-V domain orientations.

In the last decades, antibodies have emerged as one of the most important and successful classes of biopharmaceuticals. The highest variability and diversity of an antibody is concentrated on six hypervariable loops, also known as complementarity determining regions (CDRs) shaping the antigen-binding site, the paratope. Whereas it was assumed that certain sequences can only adopt a limited set of backbone conformations, in this study we present a kinetic classification of several paratope states in solution.