Structural characterization of a soluble and partially folded class I major histocompatibility heavy chain/2m heterodimer
Marlèene Bouvier1, 3
& Don C. Wiley1, 2, 4
1Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
2Howard Hughes Medical Institute, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
3Present address: University of Connecticut, Department of Pharmaceutical Sciences, 372 Fairfield Road U-92, Storrs, Connecticut 06269, USA.
4email: wiley@xtalO.harvard.edu
Class I major histocompatibility (MHC) heavy chain (HC) must fold and assemble with 2 microglobulin (2m) prior to binding peptides in the endoplasmic reticulum (ER). Each of these events is mediated by association with chaperones and other proteins and is an essential requirement for the maturation and normal cell surface expression of stable class I MHC-peptide complexes. Here we describe the biochemical and structural characterization of a soluble HC (B*0702)/2m heterodimer, apparently free of peptide. Results suggest that the peptide binding domains (1 and 2) of this folding intermediate are unstable and possess many of the properties ascribed to the molten globule state. The partially folded state of the HC/2m heterodimer is consistent with the suggestion that it is stabilized by chaperones and other proteins in the ER. This soluble intermediate may be useful for studying protein-assisted folding and peptide binding of class I MHC molecules.
2m heterodimer
2 microglobulin (
1 and 
