Coiled coils 9-to-5: rational de novo design of α-helical barrels with tunable oligomeric states
| Autor: | Guto G. Rhys, William M. Dawson, Derek N. Woolfson, Freddie J. O. Martin, R. Leo Brady, Kathryn L Shelley |
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| Rok vydání: | 2021 |
| Předmět: |
Alanine
0303 health sciences Chemistry Bristol BioDesign Institute Rational design BrisSynBio Sequence (biology) General Chemistry Crystal structure 010402 general chemistry 01 natural sciences 0104 chemical sciences Serine 03 medical and health sciences Crystallography Amphiphile Helix Side chain synthetic biology 030304 developmental biology |
| Zdroj: | Dawson, W M, Martin, F J O, Rhys, G G, Shelley, K L, Brady, R L & Woolfson, D N 2021, ' Coiled coils 9-to-5 : rational de novo design of α-helical barrels with tunable oligomeric states ', Chemical Science, vol. 12, no. 20, pp. 6923-6928 . https://doi.org/10.1039/d1sc00460c |
| ISSN: | 2041-6539 2041-6520 |
| Popis: | The 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 α-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 α-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 α-helical barrels rationalize this: side chains at Z point directly into the helical interfaces, and smaller residues allow closer helix contacts and larger assemblies. |
| Databáze: | OpenAIRE |
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