A Structurally Distinct Human Mycoplasma Protein that Generically Blocks Antigen-Antibody Union

• Published in: Science (American Association for the Advancement of Science) Vol. 343; no. 6171; pp. 656 - 661
• Main Authors: Grover, Rajesh K., Zhu, Xueyong, Nieusma, Travis, Jones, Teresa, Boero, Isabel, MacLeod, Amanda S., Mark, Adam, Niessen, Sherry, Kim, Helen J., Kong, Leopold, Assad-Garcia, Nacyra, Kwon, Keehwan, Chesi, Marta, Smider, Vaughn V., Salomon, Daniel R., Jelinek, Diane F., Kyle, Robert A., Pyles, Richard B., Glass, John I., Ward, Andrew B., Wilson, Ian A., Lerner, Richard A.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 07.02.2014; The American Association for the Advancement of Science
• Subjects: Antibodies; Antibody binding sites; Antigen-Antibody Reactions - genetics; Antigen-Antibody Reactions - immunology; Antigens; Antigens - immunology; Bacteria; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Binding sites; Crystal structure; Crystallography, X-Ray; Gels; Humans; humoral immunity; Immune response; Immune system; Immunoglobulin G - immunology; Immunoglobulin kappa-Chains - immunology; Immunoglobulin lambda-Chains - immunology; Immunoglobulin Variable Region - immunology; industry; Lymphokines - chemistry; Lymphokines - genetics; Lymphokines - immunology; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - immunology; Monoclonal antibodies; Multiple myeloma; Mycoplasma; Mycoplasma - immunology; Protein Structure, Tertiary; Proteins; Reagents; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - immunology
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1246135

We report the discovery of a broadly reactive antibody-binding protein (Protein M) from human mycoplasma. The crystal structure of the ectodomain of transmembrane Protein M differs from other known protein structures, as does its mechanism of antibody binding. Protein M binds with high affinity to all types of human and nonhuman immunoglobulin G, predominantly through attachment to the conserved portions of the variable region of the κ and λ light chains. Protein M blocks antibody-antigen union, likely because of its large C-terminal domain extending over the antibody-combining site, blocking entry to large antigens. Similar to the other immunoglobulin-binding proteins such as Protein A, Protein M as well as its orthologs in other Mycoplasma species could become invaluable reagents in the antibody field.