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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References
Germain, R. N. & Margulies, D. H. A. Rev. Immun. 11, 403–450 (1993).
Madden, D. R., Gorga, J. C., Strominger, J. L. & Wiley, D. C. Nature 353, 321–325 (1991).
Madden, D. R., Gorga, J. C., Strominger, J. L. & Wiley, D. C. Cell 70, 1035–1048 (1992).
Madden, D. R., Garboczi, D. N. & Wiley, D. C. Cell 75, 693–708 (1993).
Guo, H.-C. et al. Nature 360, 364–366 (1992).
Zhang, W., Young, A. C. M., Imarai, M., Nathenson, S. G. & Sacchettini, J. C. Proc. natn. Acad. Sci. U.S.A. 89, 8403–8407 (1992).
Fremont, D. H., Matsumura, M., Stura, E. A., Peterson, P. A. & Wilson, I. A. Science 257, 919–927 (1992).
Young, A. C. M., Zhang, W., Sacchettini, J. C. & Nathenson, S. G. Cell 76, 39–50 (1994).
Henderson, R. A. et al. Science 255, 1264–1266 (1992).
Chen, Y. et al. J. Immun. 152, 2874–2881 (1994).
Huczko, E. L. et al. J. Immun. 151, 2572–2587 (1993).
Olsen, A. C. et al. Eur. J. Immun. 24, 385–392 (1994).
Urban, R. G. et al. Proc. natn. Acad. Sci. U.S.A. 91, 1534–1538 (1994).
Bouvier, M. & Wiley, D. C. Science 265, 398–402 (1994).
Wei, M. & Cresswell, P. Nature 356, 443–446 (1992).
Rotzschke, O. et al. Nature 348, 252–254 (1990).
Brown, J. H. et al. Nature 364, 33–39 (1993).
Stern, L. J. et al. Nature 368, 215–221 (1994).
Stern, L. J. & Wiley, D. C. Structure 2, 245–251 (1994).
Garboczi, D. N., Hung, D. T. & Wiley, D. C. Proc. natn. Acad. Sci. U.S.A. 89, 3429–3433 (1992).
Harrison, S. C. J. Appl. Crystallogr. 1, 84–90 (1968).
Garboczi, D. N., Madden, D. R. & Wiley, D. C. J. molec. Biol. 239, 581–587 (1994).
Jones, T. A., Zou, J.-Y., Cowan, S. W. & Kjeldgaard, M. Acta Crystallogr. A47, 110–119 (1991).
Brünger, A. X-PLOR (version 3.0) Manual (Yale University, New Haven, Conn, 1992).
Brünger, A. T. Nature 355, 472–475 (1992).
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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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