Leucine is the most stabilizing aliphatic amino acid in the d position of a dimeric leucine zipper coiled coil.
The energetic contribution of seven amino acids in the d position of a dimeric leucine zipper coiled coil structure was measured by determining the thermal stability. The d position contains the conserved leucines found in the leucine zipper. We used a natural bZIP protein as our host-guest system that remains dimeric when a single d position is mutated. We have determined the thermal stability, monitored by circular dichroism, of 14 proteins which indicate that alanine is 4.6 kcal mol-1 per residue less stabilizing than leucine. The similarly sized amino acid isoleucine is 2.9 kcal mol-1 per residue less stabilizing than leucine, suggesting that leucine is well-packed. Model building indicates that the beta-branched amino acids isoleucine and valine in the d position produced interhelical clashes between the Cgamma2 methyl groups when placed in the favored rotamer conformation. The stabilization by leucine in different d positions is context-dependent; it varies by over 2 kcal mol-1 in the two positions examined. The order of stabilization is L, M, I, V, C, A, and S. Cysteine in the d position can form a disulfide bond which stabilizes the coiled coil.
Moitra
J
J
Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Szilák
L
L
Krylov
D
D
Vinson
C
C
D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D019281:Dimerization; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D009154:Mutation; D011489:Protein Denaturation; D013696:Temperature
D004268:DNA-Binding Proteins