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          Institute: MPI für Biochemie     Collection: Structural Biology (W. Baumeister)     Display Documents

ID: 318516.0, MPI für Biochemie / Structural Biology (W. Baumeister)
Recognition principle of the tap transporter disclosed by combinatorial peptide libraries
Authors:Uebel, S.; Kraas, W.; Kienle, S.; Wiesmüller, K. H.; Jung, G.; Tampe, R.
Date of Publication (YYYY-MM-DD):1997-08-19
Title of Journal:Proceedings of the National Academy of Sciences of the United States of America
Issue / Number:17
Start Page:8976
End Page:8981
Review Status:not specified
Audience:Not Specified
Abstract / Description:Transport of peptides across the membrane of the endoplasmic reticulum for assembly with MHC class I molecules is an essential step in antigen presentation to cytotoxic T cells, This task is performed by the major histocompatibility complex-encoded transporter associated with antigen processing (TAP). Using a combinatorial approach we have analyzed the substrate specificity of human TAP at high resolution and in the absence of any given sequence context, revealing the contribution of each peptide residue in stabilizing binding to TAP. Human TAP was found to be highly selective with peptide affinities covering at least three orders of magnitude, Interestingly, the selectivity is not equally distributed over the substrate, Only the N-terminal three positions and the C-terminal residue are critical, whereas effects from other peptide positions are negligible. A major influence from the peptide backbone was uncovered by peptide scans and libraries containing D amino acids, Again, independent of peptide length, critical positions were clustered near the peptide termini. These approaches demonstrate that human TBP is selective, with residues determining the affinity located in distinct regions, and point to the role of the peptide backbone in binding to TAP, This binding mode of TAP has implications in an optimized repertoire selection and in a coevolution with the major histocompatibility complex/T cell receptor complex. [References: 31]
Free Keywords:Abc transporter; Antigen presentation; Antigen processing; Combinatorial chemistry.; Class-i molecules; Endoplasmic-reticulum; Rma-s; Binding; Translocation; Specificity; Variants; Mouse; Expression.; Multidisciplinary.
External Publication Status:published
Document Type:Article
Communicated by:Anton Hillebrand
Affiliations:MPI für Biochemie/Structural Biology (W. Baumeister)
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