6KRV

Crystal structure of mouse IgG2b Fc complexed with B domain of Protein A

Summary for 6KRV

• Entry DOI: 10.2210/pdb6krv/pdb
• Related: 2RGS 6KRU
• Descriptor: Ig gamma-2B chain C region, Immunoglobulin G-binding protein A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: fc-fragment, immunoglobulin, immune system, protein a, b-domain
• Biological source: Staphylococcus aureus; More
• Total number of polymer chains: 4
• Total formula weight: 84239.30

Authors

Taniguchi, Y.,Satoh, T.,Yagi, H.,Kato, K. (deposition date: 2019-08-22, release date: 2020-01-22, Last modification date: 2024-11-20)

Primary citation

Yanaka, S.,Yogo, R.,Watanabe, H.,Taniguchi, Y.,Satoh, T.,Komura, N.,Ando, H.,Yagi, H.,Yuki, N.,Uchihashi, T.,Kato, K.
On-Membrane Dynamic Interplay between Anti-GM1 IgG Antibodies and Complement Component C1q.
Int J Mol Sci, 21:-, 2019

PubMed Abstract: Guillain-Barré syndrome, an autoimmune neuropathy characterized by acute limb weakness, is often preceded by infection. Molecular mimicry exists between the bacterial lipo-oligosaccharide and human ganglioside. Such infection induces production of immunoglobulin G1 (IgG1) autoantibodies against GM1 and causes complement-mediated motor nerve injury. For elucidating the molecular mechanisms linking autoantigen recognition and complement activation, we characterized the dynamic interactions of anti-GM1 IgG autoantibodies on ganglioside-incorporated membranes. Using high-speed atomic force microscopy, we found that the IgG molecules assemble into a hexameric ring structure on the membranes depending on their specific interactions with GM1. Complement component C1q was specifically recruited onto these IgG rings. The ring formation was inhibited by an IgG-binding domain of staphylococcal protein A bound at the cleft between the C2 and C3 domains. These data indicate that the IgG assembly is mediated through Fc-Fc interactions, which are promoted under on-membrane conditions due to restricted translational diffusion of IgG molecules. Reduction and alkylation of the hinge disulfide impaired IgG ring formation, presumably because of an increase in conformational entropic penalty. Our findings provide mechanistic insights into the molecular processes involved in Guillain-Barré syndrome and, more generally, into antigen-dependent interplay between antibodies and complement components on membranes.

PubMed: 31878295
DOI: 10.3390/ijms21010147

Experimental method

X-RAY DIFFRACTION (3.3 Å)