Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

AMYLOID STRUCTURE

Mimicking cross-α amyloids

Nature Chemical Biology volume 14, pages 833–834 (2018)Cite this article

Subjects

The design of spiraling cross-α amyloid-like structures reveals fascinating supermolecular fibrils of diverse compactness and stability. The small sequence variations governing cross-α self-assembly properties concur with amyloids being basic building blocks of life and natural targets for microbial structural mimicry.

In contrast to the highly stable cross-β fibrils formed via steric-zipper-like interactions, which play roles in pathological conditions or biofilm stability, several functional amyloids exhibit reversible fibril formation that is required for their activity and regulation. For example, atypical crystal structures of β-rich fibrils—indicating reduced stability compared to canonical cross-β fibrils—and reversible fibril formation were observed both for human low-complexity protein segments associated with membraneless assemblies that formed fibrils with kinked β-sheets5,6 and for a bacterial-derived antibacterial peptide that formed a β-rich hexameric arrangement yielding channels along the fibril axis2. Zhang et al.4 were able to design both stable and reversible configurations and control compactness in the spiraling cross-α assemblies via sequence variations as minor as a single residue within the 25-residue long peptides. It was overall surprising to discover that even in such robust fibrils, very few sequence substitutions translate into large changes in supramolecular structure and stability or influence their ability to assemble altogether4. For example, substituting a small residue (serine, glycine or alanine) with the intermediate-sized leucine at position 11, which mediates interhelical interactions, resulted in faster fibril formation and wider, longer fibrils. The corresponding crystal structure indicated a more loosely packed supermolecular structure compared to the peptides with smaller residues. Furthermore, peptides with phenylalanine at this position did not form fibrils, only amorphous aggregates, and failed to crystallize4. The designed peptides, when expressed in cells tagged with enhanced GFP, aggregated to form protein inclusions that appeared as bright intracellular puncta. Remarkably, the tightness of the packing observed in the crystal structures manifested in those cellular assemblies, with the densely packed structures forming immobile inclusions and the more loosely packed design being mobile4.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1: Polymorphic amyloid-like fibrils and structural mimicry.

References

  1. Eisenberg, D. S. & Sawaya, M. R. Annu. Rev. Biochem. 86, 69–95 (2017).

    Article  CAS  PubMed  Google Scholar 

  2. Salinas, N., Colletier, J. P., Moshe, A. & Landau, M. Nat. Commun. (in the press).

  3. Tayeb-Fligelman, E. et al. Science 355, 831–833 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zhang, S.-Q. Nat. Chem. Biol. https://doi.org/10.1038/s41589-018-0105-5 (2018).

  5. Hughes, M. P. et al. Science 359, 698–701 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Luo, F. et al. Nat. Struct. Mol. Biol. 25, 341–346 (2018).

    Article  CAS  PubMed  Google Scholar 

  7. Jacobs, M. D. & Harrison, S. C. Cell 95, 749–758 (1998).

    Article  CAS  PubMed  Google Scholar 

  8. Plückthun, A. Annu. Rev. Pharmacol. Toxicol. 55, 489–511 (2015).

    Article  CAS  PubMed  Google Scholar 

  9. Rout, S. K., Friedmann, M. P., Riek, R. & Greenwald, J. Nat. Commun. 9, 234 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Friedland, R. P. J. Alzheimers Dis. 45, 349–362 (2015).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, Technion – Israel Institute of Technology, Haifa, Israel

    Meytal Landau

Authors
  1. Meytal Landau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Meytal Landau.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Landau, M. Mimicking cross-α amyloids. Nat Chem Biol 14, 833–834 (2018). https://doi.org/10.1038/s41589-018-0118-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41589-018-0118-0

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing