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Title: Crystal Structures of the Staphylococcal Toxin SSL5 in Complex With Sialyl-Lewis X Reveal a Conserved Binding Site That Shares Common Features With Viral And Bacterial Sialic Acid-Binding Proteins

Abstract

Staphylococcus aureus is a significant human pathogen. Among its large repertoire of secreted toxins is a group of staphylococcal superantigen-like proteins (SSLs). These are homologous to superantigens but do not have the same activity. SSL5 is shown here to bind to human granulocytes and to the cell surface receptors for human IgA (Fc alphaRI) and P-selectin [P-selectin glycoprotein ligand-1 (PSGL-1)] in a sialic acid (Sia)-dependent manner. Co-crystallization of SSL5 with the tetrasaccharide sialyl Lewis X (sLe(X)), a key determinant of PSGL-1 binding to P-selectin, led to crystal structures of the SSL5-sLe(X) complex at resolutions of 1.65 and 2.75 A for crystals at two pH values. In both structures, sLe(X) bound to a specific site on the surface of the C-terminal domain of SSL5 in a conformation identical with that bound by P-selectin. Conservation of the key carbohydrate binding residues indicates that this ability to bind human glycans is shared by a substantial subgroup of the SSLs, including SSL2, SSL3, SSL4, SSL5, SSL6, and SSL11. This indicates that the ability to target human glycans is an important property of this group of toxins. Structural comparisons also showed that the Sia binding site in SSL5 contains a substructure that is shared bymore » other Sia binding proteins from bacteria as well as viruses and represents a common binding motif.« less

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
953964
Report Number(s):
SLAC-REPRINT-2009-428
Journal ID: ISSN 0022-2836; JMOBAK; TRN: US201004%%701
DOE Contract Number:  
AC02-76SF00515
Resource Type:
Journal Article
Journal Name:
J. Mol. Biol. 374:1293,2007
Additional Journal Information:
Journal Volume: 374; Journal Issue: 5; Journal ID: ISSN 0022-2836
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; BACTERIA; CARBOHYDRATES; CRYSTAL STRUCTURE; CRYSTALS; GLYCOPROTEINS; LEUKOCYTES; PH VALUE; PROTEINS; RECEPTORS; RESIDUES; SIALIC ACID; STAPHYLOCOCCUS; SURFACES; TOXINS; VIRUSES; Other,OTHER, BIO

Citation Formats

Baker, H M, Basu, I, Chung, M C, Caradoc-Davies, T, Fraser, J D, and Baker, E N. Crystal Structures of the Staphylococcal Toxin SSL5 in Complex With Sialyl-Lewis X Reveal a Conserved Binding Site That Shares Common Features With Viral And Bacterial Sialic Acid-Binding Proteins. United States: N. p., 2009. Web.
Baker, H M, Basu, I, Chung, M C, Caradoc-Davies, T, Fraser, J D, & Baker, E N. Crystal Structures of the Staphylococcal Toxin SSL5 in Complex With Sialyl-Lewis X Reveal a Conserved Binding Site That Shares Common Features With Viral And Bacterial Sialic Acid-Binding Proteins. United States.
Baker, H M, Basu, I, Chung, M C, Caradoc-Davies, T, Fraser, J D, and Baker, E N. 2009. "Crystal Structures of the Staphylococcal Toxin SSL5 in Complex With Sialyl-Lewis X Reveal a Conserved Binding Site That Shares Common Features With Viral And Bacterial Sialic Acid-Binding Proteins". United States.
@article{osti_953964,
title = {Crystal Structures of the Staphylococcal Toxin SSL5 in Complex With Sialyl-Lewis X Reveal a Conserved Binding Site That Shares Common Features With Viral And Bacterial Sialic Acid-Binding Proteins},
author = {Baker, H M and Basu, I and Chung, M C and Caradoc-Davies, T and Fraser, J D and Baker, E N},
abstractNote = {Staphylococcus aureus is a significant human pathogen. Among its large repertoire of secreted toxins is a group of staphylococcal superantigen-like proteins (SSLs). These are homologous to superantigens but do not have the same activity. SSL5 is shown here to bind to human granulocytes and to the cell surface receptors for human IgA (Fc alphaRI) and P-selectin [P-selectin glycoprotein ligand-1 (PSGL-1)] in a sialic acid (Sia)-dependent manner. Co-crystallization of SSL5 with the tetrasaccharide sialyl Lewis X (sLe(X)), a key determinant of PSGL-1 binding to P-selectin, led to crystal structures of the SSL5-sLe(X) complex at resolutions of 1.65 and 2.75 A for crystals at two pH values. In both structures, sLe(X) bound to a specific site on the surface of the C-terminal domain of SSL5 in a conformation identical with that bound by P-selectin. Conservation of the key carbohydrate binding residues indicates that this ability to bind human glycans is shared by a substantial subgroup of the SSLs, including SSL2, SSL3, SSL4, SSL5, SSL6, and SSL11. This indicates that the ability to target human glycans is an important property of this group of toxins. Structural comparisons also showed that the Sia binding site in SSL5 contains a substructure that is shared by other Sia binding proteins from bacteria as well as viruses and represents a common binding motif.},
doi = {},
url = {https://www.osti.gov/biblio/953964}, journal = {J. Mol. Biol. 374:1293,2007},
issn = {0022-2836},
number = 5,
volume = 374,
place = {United States},
year = {2009},
month = {6}
}