Abstract by Kimberlee Stern

Personal Infomation

Presenter's Name

Kimberlee Stern

Degree Level


Abstract Infomation


Chemistry and Biochemistry

Faculty Advisor

Josh Price


Folding of a helix bundle is stabilized by a solvent exposed non-covalent interaction


α-helical coiled coils (or helix bundles) are among the most extensively characterized tertiary/quaternary structural motifs within proteins. Folding of these helix bundles is driven by burial of non-polar amino acids at the interhelical interface; these non-polar residues typically occupy a and d positions within the repeating abcdefg heptad sequence. In contrast, many helix-bundle design efforts assume that substitutions at solvent-exposed b, c, and f positions should have minimal structural consequences. Our results challenge this assumption: here we show that solvent-exposed f-position residue14 can facilitate a stabilizing long-range synergistic interaction involving a b-position Glu10 (i.e., i–4 relative to residue 14) and c-position Lys18 (i.e., i+4) within a well-characterized trimeric helix bundle. The extent of stabilization associated with the Glu10-Lys18 pair depends primarily on the presence of a side-chain hydrogen-bond donor at residue 14. The non-polar or hydrophobic character of residue plays a smaller but still significant role.  These results suggest the need to consider substituion at these positions in helix design.