Structural disorder and dynamics of elastinThis paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular &amp; Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

Muiznieks, Lisa D.; Weiss, Anthony S.; Keeley, Fred W.

doi:10.1139/o09-161

Cited by 144 publications

(88 citation statements)

References 150 publications

(152 reference statements)

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“…Following from the results obtained from NMR transverse relaxation measurements (vide infra) and supported by previous literature results [24,26], the amino-acid elastin chains in the biohybrid microgel are composed of differently mobile hydrophobic domains and crosslinking domains. The equation of state Eq.…”

Section: Modified Flory-rehner Theory For Hydrophobic and Crosslinkinsupporting

confidence: 72%

Structural and interaction parameters of thermosensitive native α-elastin biohybrid microgel

Balaceanu

Singh

Demco

et al. 2014

Chemical Physics Letters

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Section: Modified Flory-rehner Theory For Hydrophobic and Crosslinkinsupporting

confidence: 72%

Structural and interaction parameters of thermosensitive native α-elastin biohybrid microgel

Balaceanu

Singh

Demco

et al. 2014

Chemical Physics Letters

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“…131 The idea of using flexible disorder for making sturdy complexes is illustrated by elastin, which is a self-assembling intrinsically disordered protein of elastic fibers found in the extracellular matrix and constituting an essential part of different elastic tissues in animals (e.g., connective and vascular tissue, lungs, and skin). 138 The major biological function of elastin relies on its ability to elastically extend and contract in repetitive motion when hydrated. [139][140][141][142][143] Although monomers of elastin are highly disordered, random coil-like polypeptides, 138,[144][145][146][147] because of the formation of the elastic supramolecular complexes, this protein has been shown to be one of the longest lasting proteins in the body, possessing a half-life of about 74 y.…”

Section: Making Sturdy Complexesmentioning

confidence: 99%

Paradoxes and wonders of intrinsic disorder: Stability of instability

Uversky

2017

Intrinsically Disordered Proteins

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This article continues a series of short comments on the paradoxes and wonders of the protein intrinsic disorder phenomenon by introducing the "stability of instability" paradox. Intrinsically disordered proteins (IDPs) are characterized by the lack of stable 3D-structure, and, as a result, have an exceptional ability to sustain exposure to extremely harsh environmental conditions (an illustration of the "you cannot break what is already broken" principle). Extended IDPs are known to possess extreme thermal and acid stability and are able either to keep their functionality under these extreme conditions or to rapidly regain their functionality after returning to the normal conditions. Furthermore, sturdiness of intrinsic disorder and its capability to "ignore" harsh conditions provides some interesting and important advantages to its carriers, at the molecular (e.g., the cell wall-anchored accumulation-associated protein playing a crucial role in intercellular adhesion within the biofilm of Staphylococcus epidermidis), supramolecular (e.g., protein complexes, biologic liquid-liquid phase transitions, and proteinaceous membrane-less organelles), and organismal levels (e.g., the recently popularized case of the microscopic animals, tardigrades, or water bears, that use intrinsically disordered proteins to survive desiccation).

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“…Together these residues limit the formation of extended secondary structure by preventing extensive backbone self-interactions due to the steric constraints (fixed dihedral angle and absence of amide hydrogen) imposed by prolines and the high entropic penalty for glycine confinement (6,14). Hence, these residues provide the basis for the maintenance of structural disorder and dynamics within elastin sequences (6,45). Hydrophobic elastin sequences, including tandem PGV and GVA sequence elements, transiently adopt local secondary structures such as polyproline II motifs and ␤-turns (4,26,46).…”

Section: Proline Prevents the Aggregation Of Exposed Hydrophobicmentioning

confidence: 99%

“…Influence of Proline Spacing on Polymeric Elastin AssemblyThe role for the high proportion of proline residues in elastin and other elastomeric proteins is likely related to its function as a "gatekeeper" residue, limiting the extent of sequence able to form ␤-structures, maintaining the disordered structure required for elastomeric proteins, and preventing collapse into hydrophobic cores (6,21,45). Maintenance of an average proline periodicity of ϳ6 residues across hydrophobic domains 2-24 of human tropoelastin appears to be consistent with that type of a gatekeeper role.…”

Section: Proline Prevents the Aggregation Of Exposed Hydrophobicmentioning

confidence: 99%

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

Muiznieks

Keeley

2010

Journal of Biological Chemistry

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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...

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Cited by 144 publications

References 150 publications

Structural and interaction parameters of thermosensitive native α-elastin biohybrid microgel

Structural and interaction parameters of thermosensitive native α-elastin biohybrid microgel

Paradoxes and wonders of intrinsic disorder: Stability of instability

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

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