Orthogonal packing of beta-pleated sheets in proteins.

Two classes of beta-sheet to beta-sheet packing can be distinguished in globular proteins. Both classes have beta sheets with the usual right-handed twist packed face to face. In orthogonal beta-sheet packings, the strand directions of the different beta sheets are 90 degrees to each other. Twisted beta sheets in this orientation have anticomplementary surfaces: one pair of diagonally opposite corners in the beta sheets is very close, and the other pairs of corners splay apart. At the close corners, the beta sheets are usually covalently connected: a strand that is part of one beta sheet turns through a right-handed bend to become part of the second beta sheet. The bend may occur at a beta bulge, or over a stretch of residues with a characteristic conformation, forming what we call a beta bend. Contacts between the beta sheets occur along the diagonal joining the close corners. They improve about one-fourth of the beta-sheet residues, and two-thirds of them are Val, Ile, or Leu. Elsewhere, the space between the beta sheets is filled by side chains from other parts of the protein, often alpha helices placed at the splayed corners. Examples of orthogonal beta-sheet packing are found in alcohol dehydrogenase, the acid proteases, the trypsin family, papain, staphylococcal nuclease, and thermolysin. In aligned beta-sheet packings, the angle between the strand directions of the packed beta sheets is approximately -30 degrees. In this orientation, the twisted beta-sheet surfaces are complementary. The principles governing this class of beta-sheet packings have been described previously. Here we discuss the difference and similarities of the aligned and orthogonal packing classes.