MICELLE-BOUND CONFORMATIONAL PREFERENCES OF A PEPTIDE DERIVED FROM A MURINE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE

Citation
Kl. Constantine et al., MICELLE-BOUND CONFORMATIONAL PREFERENCES OF A PEPTIDE DERIVED FROM A MURINE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE, The Journal of biological chemistry, 268(30), 1993, pp. 22830-22837
Citations number
31
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
268
Issue
30
Year of publication
1993
Pages
22830 - 22837
Database
ISI
SICI code
0021-9258(1993)268:30<22830:MCPOAP>2.0.ZU;2-K
Abstract
Models of the micelle-bound conformation of a 17-residue major histoco mpatibility complex-derived peptide, [Ala85]D(k)(69-85), have been det ermined by NMR spectroscopy and simulated annealing calculations. This peptide is a truncated, substituted version of D(k)(61-85), which is a fragment of the murine major histocompatibility complex class I mole cule H-2D(k). D(k)(61-85) has been shown to adopt an ordered conformat ion required for augmentation of insulin-stimulated glucose uptake (St agsted, J., Baase, W. A., Goldstein, A., and Olsson, L. (1991) J. Biol . Chem. 266, 12844-12847). [Ala85]D(k)(69-85) retains full biological activity. Thirty-eight converged NMR structures of [Ala85]D(k)(69-85) bound to dodecyl phosphocholine micelles have been generated. The NMR- derived models display a propensity for a type-I beta-bend involving r esidues 73-76 and an amphipathic helical region involving residues 77- 84. CD spectra yield a helical content (8% at 20-25-degrees-C) consist ent with transient, partial helix formation. The relative orientation of the beta-bend region with respect to the helical region is not well defined by the NMR data. This may reflect true heterogeneity of the m icelle-bound conformation. The NMR structures were compared with a mod el of [Ala85]D(k)(69-85) derived from the x-ray coordinates of the hum an major histocompatibility complex class I allele HLA-Aw68 (Garrett, T. P. J., Saper, M. A., Bjorkmann, P. J., Strominger, T. L., and Wiley , D. C. (1989) Nature 342, 692-696). Structural features that are impo rtant for the bioactivity of [Ala85]D(k)(69-85) are discussed with ref erence to reported structure-activity relationships (Stagsted, J., Map elli, C., Meyers, C., Matthews, B. W., Anfinsen, C. B., Goldstein, A., and Olsson, L. (1993) Proc. Natl. Acad. Sci. U. S. A., in press). A g eneral description of the structural properties of the putative recept or site(s) that are likely to be required for binding [Ala85]D(k)(6985 ) is given.