2G9H

Crystal Structure of Staphylococcal Enterotoxin I (SEI) in Complex with a Human MHC class II Molecule

Summary for 2G9H

• Entry DOI: 10.2210/pdb2g9h/pdb
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DRB1-1 beta chain, Hemagglutinin, ... (9 entities in total)
• Functional Keywords: immune system, superantigen, zn, hla clasii molecule
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P01903 P04229; Virion membrane ; Single-pass type I membrane protein : P04664
• Total number of polymer chains: 4
• Total formula weight: 70569.57

Authors

Fernandez, M.M.,Guan, R.,Malchiodi, E.L.,Mariuzza, R.A. (deposition date: 2006-03-06, release date: 2006-07-11, Last modification date: 2024-11-20)

Primary citation

Fernandez, M.M.,Guan, R.,Swaminathan, C.P.,Malchiodi, E.L.,Mariuzza, R.A.
Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule.
J.Biol.Chem., 281:25356-25364, 2006

PubMed Abstract: Superantigens are bacterial or viral proteins that elicit massive T cell activation through simultaneous binding to major histocompatibility complex (MHC) class II and T cell receptors. This activation results in uncontrolled release of inflammatory cytokines, causing toxic shock. A remarkable property of superantigens, which distinguishes them from T cell receptors, is their ability to interact with multiple MHC class II alleles independently of MHC-bound peptide. Previous crystallographic studies have shown that staphylococcal and streptococcal superantigens belonging to the zinc family bind to a high affinity site on the class II beta-chain. However, the basis for promiscuous MHC recognition by zinc-dependent superantigens is not obvious, because the beta-chain is polymorphic and the MHC-bound peptide forms part of the binding interface. To understand how zinc-dependent superantigens recognize MHC, we determined the crystal structure, at 2.0 A resolution, of staphylococcal enterotoxin I bound to the human class II molecule HLA-DR1 bearing a peptide from influenza hemagglutinin. Interactions between the superantigen and DR1 beta-chain are mediated by a zinc ion, and 22% of the buried surface of peptide.MHC is contributed by the peptide. Comparison of the staphylococcal enterotoxin I.peptide.DR1 structure with ones determined previously revealed that zinc-dependent superantigens achieve promiscuous binding to MHC by targeting conservatively substituted residues of the polymorphic beta-chain. Additionally, these superantigens circumvent peptide specificity by engaging MHC-bound peptides at their conformationally conserved N-terminal regions while minimizing sequence-specific interactions with peptide residues to enhance cross-reactivity.

PubMed: 16829512
DOI: 10.1074/jbc.M603969200

Experimental method

X-RAY DIFFRACTION (2 Å)