Analysis of the tertiary structure of protein β-sheet sandwiches

Abstract The face to face stacking of two primarily antiparallel β-sheets to form a β-sandwich occurs in several globular proteins including the domains of the immunoglobulins. We have examined the tertiary structures of ten β-sandwiches to show that they form a well-defined structural class with the following features. 1. (1) A standard packing geometry with the two twisted β-sheets separated by 8.3 to 10.3 A and rotated anticlockwise by 20 ° to 50 °. 2. (2) Common values and positions for changes in solvent accessible contact area during the condensation of β-strands → β-sheets → β-sandwich. In particular sheet stacking produces anti-complementary patterns of area changes. 3. (3) The sheet-sheet interface has a bilayer structure when medium sized residues in the two sheets stack but there is interdigitation of large and small residues in different sheets. 4. (4) The twisted nature of the β-sheet explains both the left-handed rotation between the two sheets and the observed anti-complementary pattern of area changes. These observations have been incorporated into a computer algorithm to predict the tertiary fold of β-sandwiches from primary and secondary structure.

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