skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: The Crystal Structures of EAP Domains from Staphylococcus aureus Reveal an Unexpected Homology to Bacterial Superantigens

Journal Article · · The Journal of Biological Chemistry
; ; ; ;

The Eap (extracellular adherence protein) of Staphylococcus aureus functions as a secreted virulence factor by mediating interactions between the bacterial cell surface and several extracellular host proteins. Eap proteins from different Staphylococcal strains consist of four to six tandem repeats of a structurally uncharacterized domain (EAP domain). We have determined the three-dimensional structures of three different EAP domains to 1.8, 2.2, and 1.35 {angstrom} resolution, respectively. These structures reveal a core fold that is comprised of an {alpha}-helix lying diagonally across a five-stranded, mixed {beta}-sheet. Comparison of EAP domains with known structures reveals an unexpected homology with the C-terminal domain of bacterial superantigens. Examination of the structure of the superantigen SEC2 bound to the {beta}-chain of a T-cell receptor suggests a possible ligand-binding site within the EAP domain (Fields, B. A., Malchiodi, E. L., Li, H., Ysern, X., Stauffacher, C. V., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. (1996) Nature 384, 188-192). These results provide the first structural characterization of EAP domains, relate EAP domains to a large class of bacterial toxins, and will guide the design of future experiments to analyze EAP domain structure/function relationships.

Research Organization:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
W-7405-ENG-48
OSTI ID:
885398
Report Number(s):
UCRL-JRNL-216376; TRN: US200616%%606
Journal Information:
The Journal of Biological Chemistry, Vol. 280, Issue 17
Country of Publication:
United States
Language:
English

References (48)

Superantigens: Mechanism of T-Cell Stimulation and Role in Immune Responses journal April 1991
Adherence of Staphylococcus aureus Is Enhanced by an Endogenous Secreted Protein with Broad Binding Activity journal May 1999
Crystal structure of microbial superantigen staphylococcal enterotoxin B at 1.5 Å resolution: implications for superantigen recognition by MHC class II molecules and T-cell receptors journal March 1998
Staphylococcus aureus Expresses a Major Histocompatibility Complex Class II Analog journal September 1995
Protein Structure Comparison by Alignment of Distance Matrices journal September 1993
The adhesive and immunomodulating properties of the multifunctional Staphylococcus aureus protein Eap journal October 2003
2.0 Å Crystal Structure of a Four-Domain Segment of Human Fibronectin Encompassing the RGD Loop and Synergy Region journal January 1996
Extracellular-matrix-binding proteins as targets for the prevention of Staphylococcus aureus infections journal December 1999
Analogs of Eap Protein Are Conserved and Prevalent in Clinical Staphylococcus aureus Isolates journal November 2001
Enterotoxin residues determining T-cell receptor Vβ binding specificity journal October 1992
Maximum-likelihood density modification journal August 2000
Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features journal December 1983
Structural basis of superantigen action inferred from crystal structure of toxic-shock syndrome toxin-1 journal January 1994
Crystal structure of the superantigen enterotoxin C2 from Staphylococcus aureus reveals a zinc-binding site journal August 1995
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination journal September 1998
Crystal structure of a T-cell receptor β-chain complexed with a superantigen journal November 1996
PROCHECK: a program to check the stereochemical quality of protein structures journal April 1993
A procedure for the isolation of deoxyribonucleic acid from micro-organisms journal April 1961
Netrin Binds Discrete Subdomains of DCC and UNC5 and Mediates Interactions between DCC and Heparin journal June 2003
Identification of a Staphylococcus aureus extracellular matrix-binding protein with broad specificity. journal January 1993
Evidence for three different fibrinogen-binding proteins with unique properties from Staphylococcus aureus strain Newman journal April 1992
Improved methods for building protein models in electron density maps and the location of errors in these models journal March 1991
Crystallization of a fragment of human fibronectin: Introduction of methionine by site-directed mutagenesis to allow phasing via selenomethionine journal May 1994
Structures of Five Mutants of Toxic Shock Syndrome Toxin-1 with Reduced Biological Activity † , ‡ journal May 1998
Prediction of Protein Secondary Structure at Better than 70% Accuracy journal July 1993
Crystal Structure of a Superantigen Bound to the High-Affinity, Zinc-Dependent Site on MHC Class II journal January 2001
Extracellular Adherence Protein from Staphylococcus aureus Enhances Internalization into Eukaryotic Cells journal May 2003
Staphylococcus aureus Infections journal August 1998
MSCRAMM-Mediated Adherence of Microorganisms to Host Tissues journal October 1994
Crystal structure of the streptococcal superantigen SPE-C: dimerization and zinc binding suggest a novel mode of interaction with MHC class II molecules journal August 1997
LGA: a method for finding 3D similarities in protein structures journal July 2003
Characterization of PECI, a Novel Monofunctional Δ 3 ,Δ 2 -Enoyl-CoA Isomerase of Mammalian Peroxisomes journal July 1999
The CCP4 suite programs for protein crystallography journal September 1994
Rebinding of Extracellular Adherence Protein Eap to Staphylococcus aureus Can Occur through a Surface-Bound Neutral Phosphatase journal July 2001
"Superantigens" may shed light on immune puzzle journal May 1990
MOLREP an Automated Program for Molecular Replacement journal December 1997
Molecular recognition in the post-reductionist era journal January 1999
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures journal October 1991
The role of the Map protein in Staphylococcus aureus matrix protein and eukaryotic cell adherence journal January 2002
Insertional Inactivation of eap in Staphylococcus aureus Strain Newman Confers Reduced Staphylococcal Binding to Fibroblasts journal June 2002
Structure of the Homer EVH1 Domain-Peptide Complex Reveals a New Twist in Polyproline Recognition journal April 2000
Crystal structure of a superantigen bound to MHC class II displays zinc and peptide dependence journal July 2001
Automated MAD and MIR structure solution journal April 1999
Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes journal June 2002
Superantigens as immunomodulators: recent structural insights journal August 1997
Protein secondary structure prediction based on position-specific scoring matrices 1 1Edited by G. Von Heijne journal September 1999
Receptins: a novel term for an expanding spectrum of natural and engineered microbial proteins with binding properties for mammalian proteins journal January 1999
The staphylococcal enterotoxins and their relatives journal June 1990

Similar Records

Related Subjects

36 MATERIALS SCIENCE
59 BASIC BIOLOGICAL SCIENCES
CRYSTAL STRUCTURE
DESIGN
PROTEINS
RESOLUTION
STAPHYLOCOCCUS
STRAINS
TOXINS
VIRULENCE