Suppression of conformational heterogeneity at a protein-protein interface.

Deis, Lindsay N

Wu, Qinglin

Wang, You

Qi, Yang

Daniels, Kyle G

Zhou, Pei

Oas, Terrence G

United States

2015-09-09T15:47:18Z

2015-07-21

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.

http://www.ncbi.nlm.nih.gov/pubmed/26157136

1424724112

1091-6490

https://hdl.handle.net/10161/10595

eng

Proceedings of the National Academy of Sciences

Proc Natl Acad Sci U S A

10.1073/pnas.1424724112

Staphylococcus aureus virulence

X-ray crystallography

conformational heterogeneity

immunoglobulin Fc binding

staphylococcal protein A

Amino Acid Sequence

Binding Sites

Calorimetry

Crystallography, X-Ray

Immunoglobulin Fc Fragments

Magnetic Resonance Spectroscopy

Models, Molecular

Molecular Sequence Data

Protein Binding

Protein Structure, Secondary

Solutions

Staphylococcal Protein A

Staphylococcus aureus

Structural Homology, Protein

Suppression of conformational heterogeneity at a protein-protein interface.

Journal article

Zhou, Pei|0000-0002-7823-3416

Oas, Terrence G|0000-0002-3067-2743

http://www.ncbi.nlm.nih.gov/pubmed/26157136

9028

9033

29

Basic Science Departments

Biochemistry

Chemistry

Duke

Duke Cancer Institute

Institutes and Centers

School of Medicine

Trinity College of Arts & Sciences

Published

112