EFFECT OF LOCAL SEQUENCE INVERSIONS ON THE CRYSTALLINE ANTIPARALLEL BETA-SHEET LAMELLAR STRUCTURES OF PERIODIC POLYPEPTIDES - IMPLICATIONS FOR CHAIN-FOLDING

The crystal structure and texture of the monodisperse periodic polypep tide [(AG)(3)EG(GA)(3)EG](10) (poly(+/- AG)(3)EG; A = alanine, G = gly cine, E = glutamic acid) were analyzed by X-ray diffraction, Fourier t ransform infrared spectroscopy, and electron microscopy. Structure det ermination was aided by comparison with the recently described structu re for the related periodic polypeptide [(AG)(3)EG](36) by Krejchi et al. (Macromolecules 1997;30:5012). 'Texture-oriented samples of poly(/- AG)(3)EG were obtained by crystallization of the polymer from aqueo us formic acid solution. The evidence supports an antiparallel (ap) be ta-sheet protein structure and the X-ray diffraction signals index on an orthorhombic unit cell with parameters: a=0.950 nm (hydrogen-bond d irection), b = 1.052 nm (ap beta-sheet stacking direction), c = 6.95 n m (chain direction). The absence of the (010) diffraction signal, a pr ominent signal in the poly(AG)(3)EG diffraction pattern, implies that the ap beta-sheets are 'apolar', i.e. both surfaces are equally popula ted with alanyl methyl groups. Selective line broadening of wide-angle diffraction signals with l not equal 0 gives an estimated crystal siz e of congruent to 4 nm in the chain direction. This observation, coupl ed with the appearance of low-angle particle interference peaks, indic ates a crystal thickness considerably less than the chain length and s uggests an adjacent-re-entry chain-folded lamellar structure incorpora ting the ap beta-sheet architecture. The polypeptide folds through gam ma-turns, in-phase with the pseudo-octapeptide repeat; the glutamic ac id residues occur on the lamellar surfaces. These results and those fr om the crystalline lamellae of poly(AG)(3)EG suggest that beta-turns a re not compatible with these repetitively stacked ap beta-sheet struct ures. This implies that intersheet interactions of alanyl methyl group s and glycyl alpha-protons are not sufficiently strong to dictate the folding geometry in these structures. (C) 1998 Elsevier Science B.V. A ll rights reserved.