Figure 2.
A conceptual model for chaperone recognition of the MHC-I conformational landscape. The vertical axis is free energy, and the horizontal axis shows the potential conformations that MHC-I can adopt. Unfolded or misfolded, α2 helix (denoted in red) has been shown to result in compromised TAPBPR recognition in situ [8]. However, disruption of the α1 helix does not influence TAPBPR binding [8]. MHC-I loaded with high affinity peptides may also interact with TAPBPR in an allotype-dependent manner, through the sampling of a minor, open conformation of the α2–1 helix. Introducing a disulfide linkage (Y84C/A139C) that restricts the mobility of the α2–1 helix abolishes TAPBPR binding in vitro. Figure adapted from McShan et al. (2019).