Abstract
CLASS I major histocompatibility complex (MHC) molecules present peptides to CD8+ T cells for immunological surveillance (reviewed in ref. 1). The structures of complexes of class I MHC molecules with octamer, nonamer and decamer peptides deter-mined until now2–8 show a common binding mode, with both peptide termini bound in conserved pockets at the ends of the peptide binding site. Length variations were accommodated by the peptide bulging5,6 or zig-zagging4 in the middle. Here we describe the struc-ture of a decamer peptide which binds with the carboxy-terminal residue positioned outside the peptide binding site. Several protein side chains have rearranged to allow the peptide to exit. The struc-ture suggests that even longer peptides could bind. The energetic effect of the altered mode of binding has been assessed by measur-ing the stability of the complex to thermal denaturation. Peptides bound in this novel manner are stable at physiological temperature, raising questions about their role in T-cell recognition and their production by proteolytic processing.
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Collins, E., Garboczi, D. & Wiley, D. Three-dimensional structure of a peptide extending from one end of a class I MHC binding site. Nature 371, 626–629 (1994). https://doi.org/10.1038/371626a0
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DOI: https://doi.org/10.1038/371626a0
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