| Much effort has recently been spent to understand structure-sequence relationships within a simple family of proteins, the coiled coils. The work in this thesis focuses on the role of conserved hydrophobic residues that form the "inside" of the coiled-coil fold. Experiments presented in Chapters 1 and 2 demonstrate that the shapes of these interior residues can dramatically influence the overall conformation of a coiled-coil protein. This phenomenon constitutes the clearest demonstration yet that geometric packing of apolar residues in the hydrophobic core of a protein can be an important determinant of its structure.;Because of the regularity of coiled-coils, simple and powerful computational techniques may be used to explore how interior sequence influences overall structure (Chapter 3). Predictions from such techniques match crystallographically observed conformations with surprising accuracy.;Finally, the computational methods and empirical packing rules developed from analysis of left-handed coiled coils are applied to the design of a right-handed coiled coil based on an eleven-fold hydrophobic repeat (Chapter 4). An elegant correspondence between packing in the left- and right-handed cases is observed. |
