BYU

Abstract by Taylor Loftus

Personal Infomation


Presenter's Name

Taylor Loftus

Degree Level

Undergraduate

Abstract Infomation


Department

Chemistry and Biochemistry

Faculty Advisor

Josh Price

Title

Stabilization of Helix Bundles with Solvent-Exposed Residues

Abstract

Alpha-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 inter-helical 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 substitution at these positions in helix design.