Figure 4.
Thermodynamic model for peptide exchange of major histocompatibility complex (MHC) class I. Peptide–MHC class I (pMHCI) complexes can follow two mechanistic pathways for peptide exchange starting from pMHCI ground state (state 1). In the tapasin-catalyzed pathway, tapasin modulates conformational changes in the α2-1 helix (red) of the F pocket region (pink) and the α3 domain (not shown) that accelerate the kinetics of peptide dissociation (state 2) and the loading of a high-affinity peptide (3). More intermediates states (between state 1 and state 3) need to be identified by computational studies and/or NMR and X-ray crystallography. In the non-catalyzed pathway, the peptide dissociates from the sub-optimally-loaded intermediate state (state 1′). The resulting empty MHC molecule shows subtype-dependent dynamics (especially at the F pocket region, pink) and thus can exist in a stable peptide-receptive form (state 2′) or in an unstable form (state 2″) that is chaperoned by tapasin for peptide binding. The structures used in states 1 and state 3 were modified from PDB: 1UXS (shown in white). The models used in states 1′, 2, 2′, and 2″ represent suggested states by computational and experimental studies (shown in limon).