A structural basis for Staphylococcal complement subversion

X-ray structure of the complement-binding domain of Staphylococcus aureus protein Sbi in complex with ligand C3d

Elizabeth A. Clark, Susan Crennell, Abhishek Upadhyay, Alexey V. Zozulya, Julia D. Mackay, Dimitri I. Svergun, Stefan Bagby, Jean M. H. van den Elsen

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Abstract

The structure of the complement-binding domain of Staphylococcus aureus protein Sbi (Sbi-IV) in complex with ligand C3d is presented. The 1.7 angstrom resolution structure reveals the molecular details of the recognition of thioester-containing fragment C3d of the central complement component C3, involving interactions between residues of Sbi-IV helix alpha 2 and the acidic concave surface of C3d. The complex provides a structural basis for the binding preference of Sbi for native C3 over C3b and explains how Sbi-IV inhibits the interaction between C3d and complement receptor 2. A second C3d binding site on Sbi-IV is identified in the crystal structure that is not observed in related S. aureus C3 inhibitors Efb-C and Ehp. This binding mode perhaps hints as to how Sbi-IV, as part of Sbi, forms a C3b-Sbi adduct and causes futile consumption of C3, an extraordinary aspect of Sbi function that is not shared by any other known Staphylococcal complement inhibitor.
Original languageEnglish
Pages (from-to)452-462
JournalMolecular Immunology
Volume48
Issue number4
DOIs
Publication statusPublished - Jan 2011

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Complement 3d Receptors
Complement Inactivating Agents
X-Rays
Ligands
Complement C3
Molecular Structure
Staphylococcus aureus
Binding Sites
Staphylococcus aureus Sbi protein

Cite this

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title = "A structural basis for Staphylococcal complement subversion: X-ray structure of the complement-binding domain of Staphylococcus aureus protein Sbi in complex with ligand C3d",
abstract = "The structure of the complement-binding domain of Staphylococcus aureus protein Sbi (Sbi-IV) in complex with ligand C3d is presented. The 1.7 angstrom resolution structure reveals the molecular details of the recognition of thioester-containing fragment C3d of the central complement component C3, involving interactions between residues of Sbi-IV helix alpha 2 and the acidic concave surface of C3d. The complex provides a structural basis for the binding preference of Sbi for native C3 over C3b and explains how Sbi-IV inhibits the interaction between C3d and complement receptor 2. A second C3d binding site on Sbi-IV is identified in the crystal structure that is not observed in related S. aureus C3 inhibitors Efb-C and Ehp. This binding mode perhaps hints as to how Sbi-IV, as part of Sbi, forms a C3b-Sbi adduct and causes futile consumption of C3, an extraordinary aspect of Sbi function that is not shared by any other known Staphylococcal complement inhibitor.",
author = "Clark, {Elizabeth A.} and Susan Crennell and Abhishek Upadhyay and Zozulya, {Alexey V.} and Mackay, {Julia D.} and Svergun, {Dimitri I.} and Stefan Bagby and {van den Elsen}, {Jean M. H.}",
year = "2011",
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doi = "10.1016/j.molimm.2010.09.017",
language = "English",
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TY - JOUR

T1 - A structural basis for Staphylococcal complement subversion

T2 - X-ray structure of the complement-binding domain of Staphylococcus aureus protein Sbi in complex with ligand C3d

AU - Clark, Elizabeth A.

AU - Crennell, Susan

AU - Upadhyay, Abhishek

AU - Zozulya, Alexey V.

AU - Mackay, Julia D.

AU - Svergun, Dimitri I.

AU - Bagby, Stefan

AU - van den Elsen, Jean M. H.

PY - 2011/1

Y1 - 2011/1

N2 - The structure of the complement-binding domain of Staphylococcus aureus protein Sbi (Sbi-IV) in complex with ligand C3d is presented. The 1.7 angstrom resolution structure reveals the molecular details of the recognition of thioester-containing fragment C3d of the central complement component C3, involving interactions between residues of Sbi-IV helix alpha 2 and the acidic concave surface of C3d. The complex provides a structural basis for the binding preference of Sbi for native C3 over C3b and explains how Sbi-IV inhibits the interaction between C3d and complement receptor 2. A second C3d binding site on Sbi-IV is identified in the crystal structure that is not observed in related S. aureus C3 inhibitors Efb-C and Ehp. This binding mode perhaps hints as to how Sbi-IV, as part of Sbi, forms a C3b-Sbi adduct and causes futile consumption of C3, an extraordinary aspect of Sbi function that is not shared by any other known Staphylococcal complement inhibitor.

AB - The structure of the complement-binding domain of Staphylococcus aureus protein Sbi (Sbi-IV) in complex with ligand C3d is presented. The 1.7 angstrom resolution structure reveals the molecular details of the recognition of thioester-containing fragment C3d of the central complement component C3, involving interactions between residues of Sbi-IV helix alpha 2 and the acidic concave surface of C3d. The complex provides a structural basis for the binding preference of Sbi for native C3 over C3b and explains how Sbi-IV inhibits the interaction between C3d and complement receptor 2. A second C3d binding site on Sbi-IV is identified in the crystal structure that is not observed in related S. aureus C3 inhibitors Efb-C and Ehp. This binding mode perhaps hints as to how Sbi-IV, as part of Sbi, forms a C3b-Sbi adduct and causes futile consumption of C3, an extraordinary aspect of Sbi function that is not shared by any other known Staphylococcal complement inhibitor.

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EP - 462

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

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