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Suppression of conformational heterogeneity at a protein-protein interface.

dc.contributor.author Deis, Lindsay N
dc.contributor.author Wu, Qinglin
dc.contributor.author Wang, You
dc.contributor.author Qi, Yang
dc.contributor.author Daniels, Kyle G
dc.contributor.author Zhou, Pei
dc.contributor.author Oas, Terrence G
dc.coverage.spatial United States
dc.date.accessioned 2015-09-09T15:47:18Z
dc.date.issued 2015-07-21
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/26157136
dc.identifier 1424724112
dc.identifier.uri https://hdl.handle.net/10161/10595
dc.description.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.
dc.language eng
dc.publisher Proceedings of the National Academy of Sciences
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.relation.isversionof 10.1073/pnas.1424724112
dc.subject Staphylococcus aureus virulence
dc.subject X-ray crystallography
dc.subject conformational heterogeneity
dc.subject immunoglobulin Fc binding
dc.subject staphylococcal protein A
dc.subject Amino Acid Sequence
dc.subject Binding Sites
dc.subject Calorimetry
dc.subject Crystallography, X-Ray
dc.subject Immunoglobulin Fc Fragments
dc.subject Magnetic Resonance Spectroscopy
dc.subject Models, Molecular
dc.subject Molecular Sequence Data
dc.subject Protein Binding
dc.subject Protein Structure, Secondary
dc.subject Solutions
dc.subject Staphylococcal Protein A
dc.subject Staphylococcus aureus
dc.subject Structural Homology, Protein
dc.title Suppression of conformational heterogeneity at a protein-protein interface.
dc.type Journal article
duke.contributor.id Zhou, Pei|0282523
duke.contributor.id Oas, Terrence G|0114027
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/26157136
pubs.begin-page 9028
pubs.end-page 9033
pubs.issue 29
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biochemistry
pubs.organisational-group Chemistry
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group School of Medicine
pubs.organisational-group Trinity College of Arts & Sciences
pubs.publication-status Published
pubs.volume 112
dc.identifier.eissn 1091-6490
duke.contributor.orcid Zhou, Pei|0000-0002-7823-3416
duke.contributor.orcid Oas, Terrence G|0000-0002-3067-2743


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