Many class II histocompatibility complex molecules bind antigenic peptides optimally at low pH, consistent with their exposure to antigen in acidic endosomal compartments. While it has been suggested that a partially unfolded state serves as an intermediate involved in peptide binding, very little evidence for such a state has been obtained. In this report, we show that the murine class II molecule IE becomes increasingly less stable to sodium dodecyl sulfate-induced dissociation since the pH is decreased in the same range that enhances antigenic peptide binding. Furthermore, at mildly acidic pH levels, IEk binds the fluorescent dye 1-anilino-naphthalene-8-sulfonic acid (ANS), a probe for exposed nonpolar sites in proteins, suggesting that protonation produces a molten globule-like state. The association of IEk with a single high-affinity peptide had only a small effect in these two assays, indicating that the changes that occur are distal to the peptide-binding groove. Circular dichroism analysis shows that a pH shift from neutral to mildly acidic pH causes subtle changes in the environment of aromatic residues but does not grossly disrupt the secondary structure of IEk. We propose a model in which perturbations in interdomain contacts outside the peptide-binding domain of IEk occur at acidic pH, producing a partially unfolded state that facilitates optimal antigen binding.
Article|
January 01 1996
Evidence for a conformational change in a class II major histocompatibility complex molecule occurring in the same pH range where antigen binding is enhanced.
J J Boniface,
J J Boniface
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
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D S Lyons,
D S Lyons
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
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D A Wettstein,
D A Wettstein
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
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N L Allbritton,
N L Allbritton
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
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M M Davis
M M Davis
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
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J J Boniface
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
D S Lyons
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
D A Wettstein
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
N L Allbritton
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
M M Davis
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA.
Online Issn: 1540-9538
Print Issn: 0022-1007
J Exp Med (1996) 183 (1): 119–126.
Citation
J J Boniface, D S Lyons, D A Wettstein, N L Allbritton, M M Davis; Evidence for a conformational change in a class II major histocompatibility complex molecule occurring in the same pH range where antigen binding is enhanced.. J Exp Med 1 January 1996; 183 (1): 119–126. doi: https://doi.org/10.1084/jem.183.1.119
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