4ZNC

Fc fragment of human IgG in complex with the C domain of staphylococcal protein A mutant - Q9W

Summary for 4ZNC

• Entry DOI: 10.2210/pdb4znc/pdb
• Related: 4WWI 4ZMD
• Descriptor: Immunoglobulin G-binding protein A, Ig gamma-3 chain C region (3 entities in total)
• Functional Keywords: staphylococcal protein a, spa, three-helix-bundle, antibody, igg, protein-binding domain, protein binding
• Biological source: Staphylococcus aureus; More
• Cellular location: Secreted, cell wall ; Peptidoglycan-anchor : P38507; Secreted: P01860
• Total number of polymer chains: 6
• Total formula weight: 95459.38

Authors

Deis, L.N.,Oas, T.G. (deposition date: 2015-05-04, release date: 2015-07-15, Last modification date: 2024-11-13)

Primary citation

Deis, L.N.,Wu, Q.,Wang, Y.,Qi, Y.,Daniels, K.G.,Zhou, P.,Oas, T.G.
Suppression of conformational heterogeneity at a protein-protein interface.
Proc.Natl.Acad.Sci.USA, 112:9028-9033, 2015

PubMed Abstract: Staphylococcal protein A (SpA) is an important virulence factor from Staphylococcus aureus responsible for the bacterium's evasion of the host immune system. SpA includes five small three-helix-bundle domains that can each bind with high affinity to many host proteins such as antibodies. The interaction between a SpA domain and the Fc fragment of IgG was partially elucidated previously in the crystal structure 1FC2. Although informative, the previous structure was not properly folded and left many substantial questions unanswered, such as a detailed description of the tertiary structure of SpA domains in complex with Fc and the structural changes that take place upon binding. Here we report the 2.3-Å structure of a fully folded SpA domain in complex with Fc. Our structure indicates that there are extensive structural rearrangements necessary for binding Fc, including a general reduction in SpA conformational heterogeneity, freezing out of polyrotameric interfacial residues, and displacement of a SpA side chain by an Fc side chain in a molecular-recognition pocket. Such a loss of conformational heterogeneity upon formation of the protein-protein interface may occur when SpA binds its multiple binding partners. Suppression of conformational heterogeneity may be an important structural paradigm in functionally plastic proteins.

PubMed: 26157136
DOI: 10.1073/pnas.1424724112

Experimental method

X-RAY DIFFRACTION (2.28 Å)