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Elastin phase separation — structure or disorder?

Nature Reviews Molecular Cell Biology volume 21, pages 568–569 (2020)Cite this article

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Biomolecular phase separation has captured the attention of biologists looking to explain the organization of intracellular puncta, but comparatively little attention has been paid to phase separation in extracellular structures. Glues, silks and gels are various substances exuded to the extracellular environment to create elastomers or adhesives. Specifically, liquid–liquid phase separation (LLPS) of tropoelastin monomers (elastin precursors) followed by their cross-linking forms a stable hydrated material, which has long been appreciated as essential for elastin formation in the mammalian extracellular matrix.

Given its unusual sequence, the mechanism by which tropoelastin and other elastin-like peptides phase separate and the structural changes they undergo upon LLPS and cross-linking remain unclear. Does the formation of protein secondary structures, particularly of β-sheets between monomers, explain the stability and elastic recoil of phase separated elastin? Given that the contribution of secondary structure to LLPS of disordered proteins remains hotly debated, elucidation of the structural features of phase separated elastin-like peptides by Reichheld et al. has been particularly instructive.

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References

Original articles

  • Reichheld, S. E. et al. Direct observation of structure and dynamics during phase separation of an elastomeric protein. Proc. Natl Acad. Sci. USA 114, E4408–E4415 (2017)

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  • Garcia Quiroz, F. et al. Intrinsically disordered proteins access a range of hysteretic phase separation behaviors. Sci. Adv. 5, eaax5177 (2019)

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Authors and Affiliations

  1. Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI, USA

    Nicolas Lux Fawzi

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  1. Nicolas Lux Fawzi
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Correspondence to Nicolas Lux Fawzi.

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The author is a member of the scientific advisory board for Dewpoint Therapeutics.

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Fawzi, N.L. Elastin phase separation — structure or disorder?. Nat Rev Mol Cell Biol 21, 568–569 (2020). https://doi.org/10.1038/s41580-020-00291-0

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