6q5i

Publication Abstract from PubMed

The association of amphipathic alpha helices in water leads to alpha-helical-bundle protein structures. However, the driving force for this-the hydrophobic effect-is not specific and does not define the number or the orientation of helices in the associated state. Rather, this is achieved through deeper sequence-to-structure relationships, which are increas-ingly being discerned. For example, for one structurally extreme but nevertheless ubiquitous class of bundle-the alpha-helical coiled coils-relationships have been established that discriminate between all-parallel dimers, trimers and tetramers. Association states above this are known, as are antiparallel and mixed arrangements of the helices. However, these alternative states are less-well understood. Here, we describe a synthetic-peptide system that switches be-tween parallel hexamers and various up-down-up-down tetramers in response to single-amino-acid changes and solution conditions. The main accessible states of each peptide variant are characterized fully in solution and, in most cases, to high resolution with X-ray crystal structures. Analysis and inspection of these structures helps rationalize the different states formed. This navigation of the structural landscape of alpha-helical coiled coils above the dimers and tri-mers that dominate in nature has allowed us to design rationally a well-defined and hyperstable antiparallel coiled-coil tetramer (apCC-Tet). This robust de novo protein provides another scaffold for further structural and functional designs in protein engineering and synthetic biology.

Navigating the structural landscape of de novo alpha-helical bundles.,Rhys GG, Wood CW, Beesley JL, Zaccai NR, Burton A, Brady RL, Thomson AR, Woolfson DN J Am Chem Soc. 2019 May 8. doi: 10.1021/jacs.8b13354. PMID:31066556^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.