Examination of possible structural constraints of MHC-binding peptides by assessment of their native structure within their source proteins

Ora Schueler-Furman, Yael Altuvia, Hanah Margalit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Antigenic peptides bind to major histocompatibility complex (MHC) molecules as a prerequisite for their presentation to T cells. In this study, we investigate possible structural preferences of MHC-binding peptides by examining the conformation space defined by the structures of these peptides within their native source proteins. Comparison of the conformation space of the native structures of MHC-binding nonamers and a corresponding conformation space defined by a random set of nonamers showed no significant difference. This suggests that the environment of the MHC binding groove has evolved to bind peptides with essentially any "structural background." A slight tendency for an extended β-conformation at positions 8 and 9 was observed for the set of native structures. We suggest that such a preference may facilitate the binding of the C-terminal anchor position of processed peptides into the corresponding specificity pocket. MHC-binding peptides represent examples of short subsequences that are present in two different structural environments: within their native protein and within the MHC binding groove. Comparison of the native and of the bound structure of the peptides showed that peptides up to 14 residues long may adopt different conformations within different protein environments. This has direct implications for structure prediction algorithms.

Original languageAmerican English
Pages (from-to)47-54
Number of pages8
JournalProteins: Structure, Function and Genetics
Volume45
Issue number1
DOIs
StatePublished - 1 Oct 2001

Keywords

  • Ligand binding
  • MHC restriction
  • Sequence - structure relationship
  • Structural conservation
  • T-cell immunity

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