PDBsum entry 2qej

Immune system

PDB id: 2qej

Contents

Protein chains

211 a.a. *

191 a.a. *

Ligands

NAG-NAG ×2

GOL ×5

Metals

_CA

Waters ×44

* Residue conservation analysis

PDB id:

2qej

Name:

Immune system

Title:

Crystal structure of a staphylococcus aureus protein (ssl7) in complex with fc of human iga1

Structure:

Ig alpha-1 c region. Chain: a, b. Fragment: fc region. Engineered: yes. Superantigen-like molecule 7. Chain: c, d. Fragment: set1. Synonym: ssl7. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: igha1. Expressed in: escherichia coli. Expression_system_taxid: 562. Staphylococcus aureus. Organism_taxid: 1280. Strain: strain number 4427 (gl1 isolate).

Resolution:

3.20Å R-factor: 0.229 R-free: 0.312

Authors:

P.A.Ramsland,N.Willoughby,H.M.Trist,W.Farrugia,P.M.Hogarth, J.D.Fraser,B.D.Wines

Key ref:

P.A.Ramsland et al. (2007). Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1. Proc Natl Acad Sci U S A, 104, 15051-15056. PubMed id: 17848512 DOI: 10.1073/pnas.0706028104

Date:

26-Jun-07 Release date: 18-Sep-07

Protein chains

P01876  (IGHA1_HUMAN) -  Immunoglobulin heavy constant alpha 1 from Homo sapiens

Seq: 398 a.a.

Struc: 211 a.a.*

Protein chains

No UniProt id for this chain

Struc: 191 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1073/pnas.0706028104

Proc Natl Acad Sci U S A 104:15051-15056 (2007)

PubMed id: 17848512

Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1.

P.A.Ramsland, N.Willoughby, H.M.Trist, W.Farrugia, P.M.Hogarth, J.D.Fraser, B.D.Wines.

ABSTRACT

Infection by Staphylococcus aureus can result in severe conditions such as septicemia, toxic shock, pneumonia, and endocarditis with antibiotic resistance and persistent nasal carriage in normal individuals being key drivers of the medical impact of this virulent pathogen. In both virulent infection and nasal colonization, S. aureus encounters the host immune system and produces a wide array of factors that frustrate host immunity. One in particular, the prototypical staphylococcal superantigen-like protein SSL7, potently binds IgA and C5, thereby inhibiting immune responses dependent on these major immune mediators. We report here the three-dimensional structure of the complex of SSL7 with Fc of human IgA1 at 3.2 A resolution. Two SSL7 molecules interact with the Fc (one per heavy chain) primarily at the junction between the Calpha2 and Calpha3 domains. The binding site on each IgA chain is extensive, with SSL7 shielding most of the lateral surface of the Calpha3 domain. However, the SSL7 molecules are positioned such that they should allow binding to secretory IgA. The key IgA residues interacting with SSL7 are also bound by the leukocyte IgA receptor, FcalphaRI (CD89), thereby explaining how SSL7 potently inhibits IgA-dependent cellular effector functions mediated by FcalphaRI, such as phagocytosis, degranulation, and respiratory burst. Thus, the ability of S. aureus to subvert IgA-mediated immunity is likely to facilitate survival in mucosal environments such as the nasal passage and may contribute to systemic infections.

Selected figure(s)

Figure 1.
Fig. 1. Crystal structure of SSL7 bound to Fc of human IgA1. (A) Ribbons-style representation with the IgA-Fc homodimer (heavy chains, magenta and cyan; carbohydrates, orange CPK spheres) and the two SSL7 molecules (yellow and red) with secondary structure displayed. (B) Solvent-accessible surface view of the SSL7 complex with IgA-Fc.

Figure 3.
Fig. 3. Surface views of binding regions on SSL7 and the Fc of human IgA1. (A) Residues at the interface ( 4 Å) are mapped to the molecular surfaces of the Fc (chain A, cyan; chain B, orange) and SSL7 (chain D, yellow) for one complex of SSL7 and the Fc. (B) Side view of the interaction between SSL7 and the Fc.

Figures were selected by the author.