Zinc induces dimerization of the class II major histocompatibility complex molecule that leads to cooperative binding to a superantigen

Hongmin Li, Yiwei Zhao, Yi Guo, Zhong Li, Leslie Eisele, Walid Mourad

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Dimerization of class II major histocompatibility complex (MHC) plays an important role in the MHC biological function. Mycoplasma arthritidis-derived mitogen (MAM) is a superantigen that can activate large fractions of T cells bearing specific T cell receptor Vβ elements. Here we have used structural, sedimentation, and surface plasmon resonance detection approaches to investigate the molecular interactions between MAM and the class II MHC molecule HLA-DR1 in the context of a hemagglutinin peptide-(306-318) (HA). Our results revealed that zinc ion can efficiently induce the dimerization of the HLA-DR1/HA complex. Because the crystal structure of the MAM/HLA-DR1/hemagglutinin complex in the presence of EDTA is nearly identical to the structure of the complex crystallized in the presence of zinc ion, Zn2+ is evidently not directly involved in the binding betweenMAMand HLA-DR1. Sedimentation and surface plasmon resonance studies further revealed that MAM binds the HLA-DR1/HA complex with high affinity in a 1:1 stoichiometry, in the absence of Zn 2+. However, in the presence of Zn2+, a dimerized MAM/HLA-DR1/HA complex can arise through the Zn2+-induced DR1 dimer. In the presence of Zn2+, cooperative binding of MAM to the DR1 dimer was also observed.

Original languageEnglish (US)
Pages (from-to)5991-6000
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number9
DOIs
StatePublished - Mar 2 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Zinc induces dimerization of the class II major histocompatibility complex molecule that leads to cooperative binding to a superantigen'. Together they form a unique fingerprint.

Cite this