IgG Antibodies and Protein G are Shapeshifting Proteins

Studying protein structure dynamics is key to understanding protein function modulation. Alternative protein conformations are well discriminated from each other by nanoESI mass spectrometry. The shapeshifting IgG antibodies and protein G are present as compactly folded native conformations in neutral buffered solution, identified by molecular ions with narrow charge state distributions, relatively few charges, and small collisional cross sections. Simultaneously present extended but nevertheless native conformations produced additional ions with higher charge states, different charge state distributions, and larger collisional cross sections. Computed collisional cross sections from “o-shape” and extended “I-shape” protein G 3D structures match to experimental data, indicating equilibrium, and an “o2I” flip process. Likewise, “m-shape” and “Y-shape” IgGs are two of reversibly adopted antibody conformations which interchange by an “m2Y” flip. Burying Fc receptor binding sites by adopting the m-shape prevents antibody-based initiation of humoral and cellular immune system responses prior to antigen contact. The “m2Y” flip provides robust regulation of opsonophagocytosis, an important immune system mechanism.