computer modeling in molecular biology.pdf

7 Major Histocompatibility Complex Class I Protein-Peptide Interactions 173The class I molecules of the MHC survey protein synthesis in the cytosol as ameans of signalling cell subversion by viral pathogens (Figure 7-1). Viral proteinssynthesized in the cytosol are proteolytically degraded and are actively transportedby the TAP molecules into he endoplasmic reticulum (ER). The TAP molecules aremembers are members of the ATP binding cassette super-family and are related tomolecules such as the multiple drug resistance transporters [9]. The peptide binds tonascent class I molecules in the ER, and the tripartite assembly of MHC class I heavychain, &microglobulin and peptide (Figure 7-2) egresses to the cell surface via thedefault pathway to be presented to the cytotoxic-T-lymphocyte population (CTL), asa prelude to the killing of the infected cell (see Figure 7-1). An excess of MHC class IFigure 7-1. Diagram to represent the intracellular trafficking of peptides and loaded MHCclass I molecules. The peptide fragments are derived from antigenic proteins in the cytosol byproteolysis (box labelled P). The peptide is then transported into the endoplasmic reticulum(ER) by the TAP transporters. Within the ER the three components of the nascent MHC classI molecule come together and assemble (see Figure 7-2). The folded MHC class I moleculethen egresses from the ER through the default pathway to the cell surface where it is expressedwith mature sugar moieties and replete with the antigenic peptide for presentation to theCD8' cytolytic T-lymphocytes.