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Structural and functional mosaic nature of MHC class I molecules in their peptide-free form. | LitMetric

AI Article Synopsis

Article Abstract

Despite well-organized peptide-loading mechanisms within the endoplasmic reticulum, major histocompatibility complex class I (MHC-I) molecules can be displayed on cell surfaces in peptide-free forms. Although these empty MHC-I (eMHC-I) molecules are presumably involved in physiological and pathological processes, little is known about their structures and functions due to their instability. Using bacterially expressed HLA-Cw*07:02 heavy chain and β2 microglobulin molecules, we successfully established an in vitro refolding method to prepare eMHC-I molecules in sufficient quantities for detailed structural analyses. NMR spectroscopy in conjunction with subunit-specific ¹⁵N-labeling techniques revealed that the peptide-binding domains and the adjacent regions were unstructured in the peptide-free form, while the remaining regions maintained their structural integrity. Consistent with our spectroscopic data, the eMHC-I complex could interact with leukocyte Ig-like receptor B1, but not with killer cell Ig-like receptor 2DL3. Thus, eMHC-I molecules have a mosaic nature in terms of their three-dimensional structure and binding to immunologically relevant molecules.

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http://dx.doi.org/10.1016/j.molimm.2013.03.014DOI Listing

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Despite well-organized peptide-loading mechanisms within the endoplasmic reticulum, major histocompatibility complex class I (MHC-I) molecules can be displayed on cell surfaces in peptide-free forms. Although these empty MHC-I (eMHC-I) molecules are presumably involved in physiological and pathological processes, little is known about their structures and functions due to their instability. Using bacterially expressed HLA-Cw*07:02 heavy chain and β2 microglobulin molecules, we successfully established an in vitro refolding method to prepare eMHC-I molecules in sufficient quantities for detailed structural analyses.

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