3D Structures of IgA, IgM, and Components.

Shunli Pan,Yoshiki Yamaguchi,Noriyoshi Manabe

doi:10.3390/ijms222312776

Shunli Pan, Yoshiki Yamaguchi + Show 1 more

Open Access

https://doi.org/10.3390/ijms222312776

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Abstract

Immunoglobulin G (IgG) is currently the most studied immunoglobin class and is frequently used in antibody therapeutics in which its beneficial effector functions are exploited. IgG is composed of two heavy chains and two light chains, forming the basic antibody monomeric unit. In contrast, immunoglobulin A (IgA) and immunoglobulin M (IgM) are usually assembled into dimers or pentamers with the contribution of joining (J)-chains, which bind to the secretory component (SC) of the polymeric Ig receptor (pIgR) and are transported to the mucosal surface. IgA and IgM play a pivotal role in various immune responses, especially in mucosal immunity. Due to their structural complexity, 3D structural study of these molecules at atomic scale has been slow. With the emergence of cryo-EM and X-ray crystallographic techniques and the growing interest in the structure-function relationships of IgA and IgM, atomic-scale structural information on IgA-Fc and IgM-Fc has been accumulating. Here, we examine the 3D structures of IgA and IgM, including the J-chain and SC. Disulfide bridging and N-glycosylation on these molecules are also summarized. With the increasing information of structure–function relationships, IgA- and IgM-based monoclonal antibodies will be an effective option in the therapeutic field.

Highlights

Immunoglobulins (Igs) are categorized into several classes (IgM, IgD, immunoglobulin A (IgA), Immunoglobulin G (IgG), andIgE), and all play an invaluable role in the immune response to pathogens
IgG, IgA and immunoglobulin M (IgM) are assembled into dimers or pentamers in the presence of J-chains
Without detailed knowledge of the 3D atomic structure and species differences, the development of this class of antibody therapeutics has been impeded. This situation is improving rapidly, and atomic-scale structural information on IgA and IgM molecules is available due to the use of cryogenic electron microscopy and X-ray crystallographic techniques, which reveal the mode of molecular assembly

Summary

Introduction

Immunoglobulins (Igs) are categorized into several classes (IgM, IgD, IgA, IgG, and. IgE), and all play an invaluable role in the immune response to pathogens. IgG, IgA and IgM are assembled into dimers or pentamers in the presence of J-chains They are transported to the mucosal surfaces by a secretory component (SC) as the first-line defense against infections [5]. Without detailed knowledge of the 3D atomic structure and species differences, the development of this class of antibody therapeutics has been impeded. This situation is improving rapidly, and atomic-scale structural information on IgA and IgM molecules is available due to the use of cryogenic electron microscopy (cryo-EM) and X-ray crystallographic techniques, which reveal the mode of molecular assembly. N-glycan modifications in the functions of IgM and IgA

Structure of IgA

Structure of IgM

Structure of five

Structure of mucosal

Interaction

Therapeutic Potential of IgA and IgM