Partial Dissociation of Truncated Peptides Influences the Structural Dynamics of the MHCI Binding Groove.

ABSTRACT: Antigen processing on MHCI involves the exchange of low-affinity peptides by high-affinity, immunodominant ones. This peptide editing process is mediated by tapasin and ERAAP at the peptide C- and N-terminus, respectively. Since tapasin does not contact the peptide directly, a sensing mechanism involving conformational changes likely allows tapasin to distinguish antigen-loaded MHCI molecules from those occupied by weakly bound, non-specific peptides. To understand this mechanism at the atomic level, we performed molecular dynamics simulations of MHCI allele B*44:02 loaded with peptides truncated or modified at the C- or N-terminus. We show that the deletion of peptide anchor residues leads to reversible, partial dissociation of the peptide from MHCI on the microsecond timescale. Fluctuati

SUBMITTER: Fisette O 

PROVIDER: S-EPMC5394104 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature