Domain 26 of Tropoelastin Plays a Dominant Role in Association by Coacervation

Jensen, Sacha A.; Vrhovski, Bernadette; Weiss, Anthony S.

doi:10.1074/jbc.m004265200

Cited by 63 publications

(85 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may be attributed to the presence of a single arginine residue near the N terminus of domain 26, which lowers the hydropathy of the sequence. In agreement with its solvent-exposed location within the full-length elastin monomer (24), this residue is likely to confer protection from aggregation on the basis of charge and high conformational entropy (50,51).…”

Section: Proline Prevents the Aggregation Of Exposed Hydrophobicmentioning

confidence: 75%

“…However, beyond domain 24, proline spacing in hydrophobic domains of human tropoelastin increases, and the data presented here demonstrate that elastin-like polypeptides allowing such increased proline spacing show both aberrant coacervation behavior and the capability of forming at least limited ␤-sheet structure. Others have also reported altered coacervation behavior associated with increased ␤-sheet in elastin-like polypeptides corresponding to sequences downstream of domain 24 (24) and in full-length tropoelastin upon mutation of a single proline to glycine in exon 26, extending a proline-free region (2). Domain 30 provides a particular example of an extended, repeated hydrophobic sequence with low proline content.…”

Section: Proline Prevents the Aggregation Of Exposed Hydrophobicmentioning

confidence: 99%

“…However, the contribution of individual hydrophobic domains to assembly is not equal (2,4,14,22,24). Given the high PG composition (2PϩG Ͼ 0.6) within a diverse range of elastomeric sequences, including hydrophobic elastin domains (6), and the importance of proline residues in modulating structural properties, we mapped the distribution of proline within each continuous hydrophobic interval of human tropoelastin (Fig.…”

Section: Distribution Of Proline Residues In Hydrophobic Sequencesmentioning

confidence: 99%

See 2 more Smart Citations

Proline Periodicity Modulates the Self-assembly Properties of Elastin-like Polypeptides

Muiznieks

Keeley

2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Elastin is a self-assembling protein of the extracellular matrix that provides tissues with elastic extensibility and recoil. The monomeric precursor, tropoelastin, is highly hydrophobic yet remains substantially disordered and flexible in solution, due in large part to a high combined threshold of proline and glycine residues within hydrophobic sequences. In fact, proline-poor elastin-like sequences are known to form amyloidlike fibrils, rich in ␤-structure, from solution. On this basis, it is clear that hydrophobic elastin sequences are in general optimized to avoid an amyloid fate. However, a small number of hydrophobic domains near the C terminus of tropoelastin are substantially depleted of proline residues. Here we investigated the specific contribution of proline number and spacing to the structure and self-assembly propensities of elastin-like polypeptides. Increasing the spacing between proline residues significantly decreased the ability of polypeptides to reversibly self-associate. Real-time imaging of the assembly process revealed the presence of smaller colloidal droplets that displayed enhanced propensity to cluster into dense networks. Structural characterization showed that these aggregates were enriched in ␤-structure but unable to bind thioflavin-T. These data strongly support a model where proline-poor regions of the elastin monomer provide a unique contribution to assembly and suggest a role for localized ␤-sheet in mediating self-assembly interactions.Elastin is the extracellular matrix protein responsible for the elasticity of vertebrate arterial vessels, connective tissues, lung, and skin. Elastin resilience is afforded by the formation of insoluble fibers, the first step of which involves the selfalignment of elastin monomers, tropoelastin, in a temperature-induced transition known as coacervation, through the association of hydrophobic domains (1, 2). Although highly (Ͼ75%) non-polar in character, tropoelastin remains predominantly monomeric and structurally disordered in solution (3-5) and critically, retains substantial backbone hydration and flexibility even when assembled (6) and cross-linked into mature, polymeric elastic arrays (7-13).Maintenance of structural heterogeneity and dynamics of the elastin backbone is achieved in large part by a high proportional composition of both proline (14%) and glycine (35%) residues within hydrophobic sequences (6, 14). These residues are commonly arranged into repeated motifs based on recurring sequence elements such as PGV and GVA. This includes a seven-fold tandem PGVGVA repeat in domain 24 of the native human elastin sequence (15). Contrary to enhancing coacervation or elastomeric properties, the multiple substitution of glycine residues for prolines within tandem repeat sequences (e.g. PGVGVA to GGVGVA) results in the formation of amyloid-like fibrils, rich in ␤-structure, from solution (6, 14). These structures are conformationally more restricted than native elastomeric sequences as a result of the tighter packing of residues into extended...

show abstract

Section: Proline Prevents the Aggregation Of Exposed Hydrophobicmentioning

confidence: 75%

Section: Proline Prevents the Aggregation Of Exposed Hydrophobicmentioning

confidence: 99%

Section: Distribution Of Proline Residues In Hydrophobic Sequencesmentioning

confidence: 99%

See 1 more Smart Citation

Proline Periodicity Modulates the Self-assembly Properties of Elastin-like Polypeptides

Muiznieks

Keeley

2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The bands close to the parent molecule result from alternative splicing, which is tissue and age specific [46][47][48][49][50][51]. Major bands at ~55 kDa, ~45 kDa, ~25 kDa and ~15 kDa are degradation products resulting from cleavage by tryptic-like proteases [25,[52][53][54]. Extreme care must be taken during tropoelastin purification and storage to include protease inhibitors in all extraction, purification, and storage buffers to prevent proteolytic breakdown.…”

Section: Isolation and Purification Of Tropoelastinmentioning

confidence: 99%

Methods in elastic tissue biology: Elastin isolation and purification

Mecham

2008

Methods

View full text Add to dashboard Cite

Elastin provides recoil to tissues subjected to repeated stretch, such as blood vessels and the lung. It is encoded by a single gene in mammals and is secreted as a 60-70 kDa monomer call tropoelastin. The functional form of the protein is that of a large, highly crosslinked polymer that organizes as sheets or fibers in the extracellular matrix. Purification of mature, crosslinked elastin is problematic because its insolubility precludes its isolation using standard wet-chemistry techniques. Instead, relatively harsh experimental approaches designed to remove non-elastin 'contaminates' are employed to generate an insoluble product that has the amino acid composition expected of elastin. Although soluble, tropoelastin also presents problems for isolation and purification. The protein's extreme stickiness and susceptibility to proteolysis requires careful attention during purification and in tropoelastin-based assays. This article describes the most common approaches for purification of insoluble elastin and tropoelastin. It also addresses key aspects of studying tropoelastin production in cultured cells, where elastin expression is highly dependent upon cell type, culture conditions, and passage number.

show abstract

“…The repetitive ELP phenomenon was inspired from W4 domain of human tropoelastin that consists of repetitive VPGG, VPGVG and APGVGV peptides (Rapaka & Urry, 1978;Jensen et al, 2000;Toonkool et al, 2001).…”

Section: The Origin and Main Properties Of Elpsmentioning

confidence: 99%

Elastin-like polypeptides and their applications in anticancer drug delivery systems: a review

Saxena

Nanjan

2013

Drug Delivery

View full text Add to dashboard Cite

Elastin-like polypeptides (ELPs) are large molecular weight biopolymers. They have been widely studied as macromolecular carriers for targeted delivery of drugs. The aim of the present article is to review the available information on ELPs (including our recent investigations), their properties, drug delivery applications to tumor sites and future perspectives. This review also provides information on the use of short synthetic ELPs for making ELP-drug conjugates, for targeted delivery of anticancer drugs. In the present review we also focus on the point that short ELPs can also be used for targeting anticancer drugs to tumor sites as they behave similar to long ELPs regarding their capacity to undergo inverse temperature transition (ITT) behavior.

show abstract

Domain 26 of Tropoelastin Plays a Dominant Role in Association by Coacervation

Cited by 63 publications

References 34 publications

Proline Periodicity Modulates the Self-assembly Properties of Elastin-like Polypeptides

Proline Periodicity Modulates the Self-assembly Properties of Elastin-like Polypeptides

Methods in elastic tissue biology: Elastin isolation and purification

Elastin-like polypeptides and their applications in anticancer drug delivery systems: a review

Contact Info

Product

Resources

About