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

Schueler-Furman, O Altuvia, Y Margalit, H

O. Schueler-furman et al., Examination of possible structural constraints of MHC-binding peptides by assessment of their native structure within their source proteins, PROTEINS, 45(1), 2001, pp. 47-54

45

INGLESE

Article

Biochemistry & Biophysics

PROTEINS-STRUCTURE FUNCTION AND GENETICS

0887-3585 → ACNP

45

1

2001

47 - 54

ISI

0887-3585(20011001)45:1<47:EOPSCO>2.0.ZU;2-M

Antigenic peptides bind to major histocompatibility complex (MHC) molecules as a prerequisite for their presentation to T cells. In this study, we inv estigate possible structural preferences of MHC-binding peptides by examini ng the conformation space defined by the structures of these peptides withi n their native source proteins. Comparison of the conformation space of the native structures of MHC-binding nonamers and a corresponding con-formatio n space defined by a random set of nonamers showed no significant differenc e. This suggests that the environment of the MHC binding groove has evolved to bind peptides with essentially any "structural background." A slight te ndency for an extended beta -conformation at positions 8 and 9 was observed for the set of native structures. We suggest that such a preference may fa cilitate the binding of the C-terminal anchor position of processed peptide s into the corresponding specificity pocket. MHC-binding peptides represent examples of short subsequences that are present in two different structura l environments: within their native protein and within the MHC binding groo ve. Comparison of the native and of the bound structure of the peptides sho wed that peptides up to 14 residues long may adopt different conformations within different protein environments. This has direct implications for str ucture prediction algorithms. (C) 2001 Wiley-Liss, Inc.