Structural highlights
Publication Abstract from PubMedThe rational design of linear peptides that assemble controllably and predictably in water is challenging. Short sequences must encode unique target structures and avoid alternative states. However, the non-covalent forces that stabilize and discriminate between states are weak. Nonetheless, for alpha-helical coiled-coil assemblies considerable progress has been made in rational de novo design. In these, sequence repeats of nominally hydrophobic (h) and polar (p) residues, hpphppp, direct the assembly of amphipathic helices into dimeric to tetrameric bundles. Expanding this pattern to hpphhph can produce larger alpha-helical barrels. Here, we show that pentameric to nonameric barrels are accessed by varying the residue at one of the h sites. In peptides with four L/I-K-E-I-A-x-Z repeats, decreasing the size of Z from threonine to serine to alanine to glycine gives progressively larger oligomers. X-ray crystal structures of the resulting alpha-helical barrels rationalize this: side chains at Z point directly into the helical interfaces, and smaller residues allow closer helix contacts and larger assemblies. Coiled coils 9-to-5: rational de novo design of alpha-helical barrels with tunable oligomeric states.,Dawson WM, Martin FJO, Rhys GG, Shelley KL, Brady RL, Woolfson DN Chem Sci. 2021 Apr 13;12(20):6923-6928. doi: 10.1039/d1sc00460c. eCollection 2021, May 26. PMID:34745518[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
This page was last modified 14:10, 17 November 2021.