Coacervation of tropoelastin

Yeo, Giselle C.; Keeley, Fred W.; Weiss, Anthony S.

doi:10.1016/j.cis.2010.10.003

Cited by 223 publications

(311 citation statements)

References 140 publications

Supporting

Mentioning

302

Contrasting

Order By: Relevance

“…Given that DgHBP-pep is strongly hydrophobic (Supplementary Fig. 6) and that optimal selfcoacervation happens when the peptide is uncharged, it follows that coacervation of the peptide is strongly influenced by hydrophobic inter actions in a manner similar to that of tropoelastin 26,42 . Furthermore, optical microscopy detected a tendency toward precipitation over time, perhaps indicating that DgHBP coacervates are in a metastable state that the animal may control kinetically in order to trigger precipitation before final curing.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the theoretical pIs of DgCBPs and DgHBPs (~8.8 and ~6.3, respectively) indicate that there is no pH window in which these proteins would be oppositely charged with a high enough charge density to form complex coacervates. On the other hand, we noticed that the modular domains of DgHBPs, comprising pentapeptides such as GHGXY (where X is often valine (Val; V) or leucine (Leu; L)), share intriguing homology with the Gly-and Val-rich hydrophobic sequence repeats of elastin 25 , which are well-known to drive selfcoacervation of tropoelastin proteins 26 via hydrophobic interactions, a mechanism that was also recently established for the mussel adhesive foot protein, Mfp-3S 27 .…”

Section: Self-coacervation Of Recombinant Dghbp-1mentioning

confidence: 99%

See 1 more Smart Citation

Infiltration of chitin by protein coacervates defines the squid beak mechanical gradient

et al. 2015

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Self-coacervation Of Recombinant Dghbp-1mentioning

confidence: 99%

Infiltration of chitin by protein coacervates defines the squid beak mechanical gradient

et al. 2015

View full text Add to dashboard Cite

“…99). Exposed hydrophobic domains interact in an entropically-driven process, resulting in lysine residues aligning in readiness for LOX-mediated cross-linking.…”

Section: Elastic Fibre Formationmentioning

confidence: 99%

Elastic fibres in health and disease

Baldwin

Simpson

Steer

et al. 2013

Expert Rev. Mol. Med.

243

158

View full text Add to dashboard Cite

Elastic fibres are insoluble components of the extracellular matrix of dynamic connective tissues such as skin, arteries, lungs and ligaments. They are laid down during development, and comprise a cross-linked elastin core within a template of fibrillin-based microfibrils. Their function is to endow tissues with the property of elastic recoil, and they also regulate the bioavailability of transforming growth factor β. Severe heritable elastic fibre diseases are caused by mutations in elastic fibre components; for example, mutations in elastin cause supravalvular aortic stenosis and autosomal dominant cutis laxa, mutations in fibrillin-1 cause Marfan syndrome and Weill–Marchesani syndrome, and mutations in fibulins-4 and -5 cause autosomal recessive cutis laxa. Acquired elastic fibre defects include dermal elastosis, whereas inflammatory damage to fibres contributes to pathologies such as pulmonary emphysema and vascular disease. This review outlines the latest understanding of the composition and assembly of elastic fibres, and describes elastic fibre diseases and current therapeutic approaches.

show abstract

“…Conversely, simple coacervation is considered an entropically driven process that depends entirely on hydrophobic interactions between protein chains (4, 16), although few molecular details of this process have been reported. Thus, a detailed understanding of protein structure and dynamics during LLPS is needed to better define the principles governing protein phase separation and to further develop applications of this type of self-assembly in biomaterial design.The elastin monomer, tropoelastin, undergoes a wellcharacterized lower critical solution temperature (LCST) phase transition that is promoted by the presence of salt and heat (8,17,18). Tropoelastin is an IDP consisting of an alternating arrangement of hydrophobic domains (HDs) and cross-linking domains (CLDs) (7,19).…”

mentioning

confidence: 99%

Direct observation of structure and dynamics during phase separation of an elastomeric protein

Reichheld

Muiznieks

Keeley

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

225

245

View full text Add to dashboard Cite

Despite its growing importance in biology and in biomaterials development, liquid-liquid phase separation of proteins remains poorly understood. In particular, the molecular mechanisms underlying simple coacervation of proteins, such as the extracellular matrix protein elastin, have not been reported. Coacervation of the elastin monomer, tropoelastin, in response to heat and salt is a critical step in the assembly of elastic fibers in vivo, preceding chemical crosslinking. Elastin-like polypeptides (ELPs) derived from the tropoelastin sequence have been shown to undergo a similar phase separation, allowing formation of biomaterials that closely mimic the material properties of native elastin. We have used NMR spectroscopy to obtain site-specific structure and dynamics of a self-assembling elastin-like polypeptide along its entire self-assembly pathway, from monomer through coacervation and into a cross-linked elastic material. Our data reveal that elastin-like hydrophobic domains are composed of transient β-turns in a highly dynamic and disordered chain, and that this disorder is retained both after phase separation and in elastic materials. Cross-linking domains are also highly disordered in monomeric and coacervated ELP 3 and form stable helices only after chemical cross-linking. Detailed structural analysis combined with dynamic measurements from NMR relaxation and diffusion data provides direct evidence for an entropy-driven mechanism of simple coacervation of a protein in which transient and nonspecific intermolecular hydrophobic contacts are formed by disordered chains, whereas bulk water and salt are excluded.phase separation | elastin | NMR | protein structure | dynamics T he liquid-liquid phase separation (LLPS) of molecules has long been exploited to concentrate and encapsulate molecules for drug delivery and food preparation (1, 2). In biology, there is increasing awareness that many proteins exhibit this type of phase behavior, allowing transient microenvironments to be quickly assembled and disassembled in response to changing solution conditions, or the availability of binding partners (3, 4). Protein phase separation occurs intracellularly to generate various membraneless organelles, such as ribonucleoprotein (RNP) bodies involved in nucleic acid processing, transport, and storage (5). A similar phenomenon is observed in the extracellular matrix as a critical step in the synthesis of elastic fibers, which provide extensibility, recoil, and resilience to tissues (6, 7). In the latter system, LLPS of monomeric elastin results in hydrated protein-rich coacervate droplets that are deposited and crosslinked to form an elastic matrix (7,8). In addition to their fundamental importance to biology, the dynamic reversibility of LLPS makes phase-separated states of proteins an attractive platform for development of responsive biomaterials with broad application, for instance as scaffolds for tissue engineering or as carriers in drug delivery systems (9-11).Despite the keen interest in proteins that undergo s...

show abstract

Coacervation of tropoelastin

Cited by 223 publications

References 140 publications

Infiltration of chitin by protein coacervates defines the squid beak mechanical gradient

Infiltration of chitin by protein coacervates defines the squid beak mechanical gradient

Elastic fibres in health and disease

Direct observation of structure and dynamics during phase separation of an elastomeric protein

Contact Info

Product

Resources

About