Suppression of conformational heterogeneity at a protein-protein interface.
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.
Type
Journal articleSubject
Staphylococcus aureus virulenceX-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
Permalink
https://hdl.handle.net/10161/10595Published Version (Please cite this version)
10.1073/pnas.1424724112Publication Info
Deis, Lindsay N; Wu, Qinglin; Wang, You; Qi, Yang; Daniels, Kyle G; Zhou, Pei; & Oas,
Terrence G (2015). Suppression of conformational heterogeneity at a protein-protein interface. Proc Natl Acad Sci U S A, 112(29). pp. 9028-9033. 10.1073/pnas.1424724112. Retrieved from https://hdl.handle.net/10161/10595.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Terrence Gilbert Oas
Professor of Biochemistry
Our laboratory is primarily interested in the mechanisms of protein folding. We use
nuclear magnetic resonance (NMR) and other types of spectroscopy to study the solution
structure, stability and folding reactions of small protein models. These include
monomeric λ repressor, the B domain of protein A (BdpA) and various regulator
of G-protein signalling (RGS) domains. Our biophysical studies are used to inform
our investigations of the role of folding mechanism in the function of pro
Pei Zhou
Professor of Biochemistry
Protein-protein interactions play a pivotal role in the regulation of various cellular
processes. The formation of higher order protein complexes is frequently accompanied
by extensive structural remodeling of the individual components, varying from domain
re-orientation to induced folding of unstructured elements. Nuclear Magnetic Resonance
(NMR) spectroscopy is a powerful tool for macromolecular structure determination in
solution. It has the unique advantage of being capable of elucidati
Alphabetical list of authors with Scholars@Duke profiles.

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info
Related items
Showing items related by title, author, creator, and subject.
-
LKB1 Loss induces characteristic patterns of gene expression in human tumors associated with NRF2 activation and attenuation of PI3K-AKT.
Kaufman, Jacob M; Amann, Joseph M; Park, Kyungho; Arasada, Rajeswara Rao; Li, Haotian; Shyr, Yu; Carbone, David P (Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2014-06)Inactivation of serine/threonine kinase 11 (STK11 or LKB1) is common in lung cancer, and understanding the pathways and phenotypes altered as a consequence will aid the development of targeted therapeutic strategies. Gene ... -
Amino acid permeases require COPII components and the ER resident membrane protein Shr3p for packaging into transport vesicles in vitro.
Kuehn, MJ; Schekman, R; Ljungdahl, PO (J Cell Biol, 1996-11)In S. cerevisiae lacking SHR3, amino acid permeases specifically accumulate in membranes of the endoplasmic reticulum (ER) and fail to be transported to the plasma membrane. We examined the requirements of transport of the ... -
G protein beta gamma subunits stimulate phosphorylation of Shc adapter protein.
Touhara, K; Hawes, BE; van Biesen, T; Lefkowitz, RJ (Proc Natl Acad Sci U S A, 1995-09-26)The mechanism of mitogen-activated protein (MAP) kinase activation by pertussis toxin-sensitive Gi-coupled receptors is known to involve the beta gamma subunits of heterotrimeric G proteins (G beta gamma), p21ras activation, ...