Suppression of conformational heterogeneity at a protein–protein interface
- Duke Univ., Durham, NC (United States)
Staphylococcal protein A (SpA) is an important virulence factor fromStaphylococcus aureusresponsible 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. As a result, suppression of conformational heterogeneity may be an important structural paradigm in functionally plastic proteins.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE
- Grant/Contract Number:
- W-31-109-Eng-38; R01-GM081666
- OSTI ID:
- 1239417
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, Issue 29; ISSN 0027-8424
- Publisher:
- National Academy of SciencesCopyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
Web of Science
Similar Records
The Crystal Structures of EAP Domains from Staphylococcus aureus Reveal an Unexpected Homology to Bacterial Superantigens
Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs