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Sites on TAPBPR that scaffold assembly of a MHC-I H chain with beta2m are important for TAPBPR chaperone activity

ABSTRACT: TAP-binding protein-related (TAPBPR) facilitates the processing of nascent class I MHC (MHC-I) by (1, chaperone function) acting as a chaperone for misfolded or partially folded MHC-I substrates in the cell and (2, editing function) by catalyzing exchange of low affinity for high affinity antigenic peptides in the MHC-I peptide-binding groove. In cells in which the principal MHC-I-specific chaperone and TAPBPR homologue tapasin has been knocked out, the processing and surface trafficking of the human MHC-I allele HLA-A2 is substantially reduced. Over-expression of TAPBPR can partially replace tapasin and rescue HLA-A2 surface expression. Using this assay as the basis for a fluorescence-based selection, TAPBPR was deep mutationally scanned at 92 positions in the core, at the interface with MHC-I, and on the ‘backside’ distal from where MHC-I binds. Critical regions of TAPBPR for rescue of HLA-A2 processing map to sites that contact the underside of the MHC-I alpha-2 domain and residues that contact the junction between beta-2 microglobulin and alpha-3 domains. Key sites on TAPBPR for chaperone activity therefore scaffold assembly of the MHC-I H chain with beta-2 microglobulin.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147137 | GEO | 2020/03/18

REPOSITORIES: GEO

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A deep mutational scan of the MHC class I-specific chaperone tapasin

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Sites on TAPBPR that scaffold assembly of a MHC-I H chain with beta2m are important for TAPBPR chaperone activity

Project description:Sites on TAPBPR that scaffold assembly of a MHC-I H chain with beta2m are important for TAPBPR chaperone activity

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