Elastin‐like polypeptides as models of intrinsically disordered proteins

Abstract

Elastin-like polypeptides (ELPs) are a class of stimuli-responsive biopolymers inspired by the intrinsically disordered domains of tropoelastin that are composed of repeats of the VPGXG pentapeptide motif, where X is a “guest residue”. They undergo a reversible, thermally triggered lower critical solution temperature (LCST) phase transition, which has been utilized for a variety of applications including protein purification, affinity capture, immunoassays, and drug delivery. ELPs have been extensively studied as protein polymers and as biomaterials, but their relationship to other disordered proteins has heretofore not been established. The biophysical properties of ELPs that lend them their unique material behavior are similar to the properties of many intrinsically disordered proteins (IDP). Their low sequence complexity, phase behavior, and elastic properties make them an interesting “minimal” artificial IDP, and the study of ELPs can hence provide insights into the behavior of other more complex IDPs. Motivated by this emerging realization of the similarities between ELPs and IDPs, this review discusses the biophysical properties of ELPs, their biomedical utility, and their relationship to other disordered polypeptide sequences.

Pipeline to Identify Hydroxyproline-Rich Glycoproteins

“…Features of other IDPs can be incorporated into MAAB and used to identify IDPs in available genomes/transcriptomes. This would allow the identification of, for example, the repetitive domains of elastins (Roberts et al, 2015), salivary PRPs (Manconi et al, 2016), insect silks (Starrett et al, 2012), AGL proteins from arbuscular mycorrhizal fungi (Schultz and Harrison, 2008), and LATE EMBRYOGENESIS ABUNDANT proteins in plants (Sun et al, 2013), with low rates of false negatives and false positives.…”

Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity

“…1a). Although ELPs and phase-separating intracellular IDPs differ substantially in their sequence composition, their sequences share three key features: (1) highly repetitive, (2) of low complexity and (3) enriched in a limited set of similar disorder-promoting amino acids), which leads to a high propensity for chain disorder in solution 15 . ELPs are SLCs that comprise pentameric repeats of Val-Pro-Gly-X 1 -Gly, where X 1 is a guest residue that can be used to modulate protein-phase behaviour 16 .…”

Single nucleotide polymorphisms and domain/splice variants modulate assembly and elastomeric properties of human elastin. Implications for tissue specificity and durability of elastic tissue

“…Given the modular domain structure of tropoelastin and the correspondence between domains and exons in the gene, loss or gain of exons/domains could be expected to lead to modified crosslinking patterns, with consequent changes in the architecture of the polymeric matrix and its properties. [37][38][39][40] Databases such as dbSNP and ExAC have documented more than 200 nonsynonymous polymorphisms affecting coding sequences of hTE, including the nonsense and missense mutations resulting in SVAS and ADCL. There are several examples of single nucleotide polymorphisms (SNPs) generating premature stop codons and resulting in loss of a functional elastin allele.…”