Structural specificity in coiled coils : a and d position polar residues
Author(s)Akey, David L. (David Lloyd), 1967-
Massachusetts Institute of Technology. Dept. of Biology.
Peter S. Kim.
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Experimental studies were performed to determine the effects of single polar residues at the a and the d positions of a reference coiled coil, GCN4-pVL. The reference coiled coil is very stable in solution and exists as a mixture of dimers and trimers. The placement of single polar residues in the otherwise hydrophobic core of GCN4-pVL has dramatic effects on both stability and oligomeric specificity. The effects vary with regard to both the identity and the position (a vs d position) of the polar substitution. The d position is more sensitive to polar residues. Two residues, asparagine and glutamine, were found to be much more destabilizing when placed at d positions than any residues at the a positions. In addition to the known ability of a single asparagine at the a position to specify coiled-coil dimers, it was found that a single threonine at the d postion can specify a coiled-coil trimer. The crystal structures of four coiled coils, with either a single serine or threonine at either the a or the d position, were determined. These structures show that threonine residues tend to form intra-helical hydrogen bonds when packed in the coiled-coil core. Serine residues tend to show more variability in their packing when placed in the core positions. Polar residues can affect the local coiled-coil geometry. The most dramatic effect was as a result of serine residues at the d position in which in a local decrease in the supercoil radius of 0.5A centered around the buried serine position was observed.
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2001.Includes bibliographical references.
DepartmentMassachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology