Antibodies, Vol. 12, Pages 67: Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines

Antibodies, Vol. 12, Pages 67: Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines

Antibodies doi: 10.3390/antib12040067

Authors: Monica L. Fernández-Quintero Nancy D. Pomarici Anna-Lena M. Fischer Valentin J. Hoerschinger Katharina B. Kroell Jakob R. Riccabona Anna S. Kamenik Johannes R. Loeffler James A. Ferguson Hailee R. Perrett Klaus R. Liedl Julianna Han Andrew B. Ward

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. We emphasize the importance of considering antibodies as conformational ensembles in solution instead of focusing on single-static structures because their functions and properties are strongly governed by their dynamic nature. Thus, in this review, we provide an overview of the unique structural and dynamic characteristics of antibodies with respect to their antigen recognition, biophysical properties, and effector functions. We highlight the numerous technical advances in antibody structure prediction and design, enabled by the vast number of experimentally determined high-quality structures recorded with cryo-EM, NMR, and X-ray crystallography. Lastly, we assess antibody and vaccine design strategies in the context of structure and dynamics.