Maintaining and breaking symmetry in homomeric coiled-coil assemblies.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30297707.
- Also identified by DOI 10.1038/s41467-018-06391-y and PMC identifier 6175849.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
In coiled-coil (CC) protein structures α-helices wrap around one another to form rope-like assemblies. Most natural and designed CCs have two-four helices and cyclic (C<sub>n</sub>) or dihedral (D<sub>n</sub>) symmetry. Increasingly, CCs with five or more helices are being reported. A subset of these higher-order CCs is of interest as they have accessible central channels that can be functionalised; they are α-helical barrels. These extended cavities are surprising given the drive to maximise buried hydrophobic surfaces during protein folding and assembly in water. Here, we show that α-helical barrels can be maintained by the strategic placement of β-branched aliphatic residues lining the lumen. Otherwise, the structures collapse or adjust to give more-complex multi-helix assemblies without C<sub>n</sub> or D<sub>n</sub> symmetry. Nonetheless, the structural hallmark of CCs-namely, knobs-into-holes packing of side chains between helices-is maintained leading to classes of CCs hitherto unobserved in nature or accessed by design.
Medical subject headings
- Models, Molecular
- Protein Folding
- Protein Multimerization
- Protein Structure, Secondary