Elastin hydrophobic domains

Tropoelastin is the soluble precursor of elastin and consists of alternating hydrophobic and hydrophilic peptide domains. The most common amino acids in the hydrophobic domains are Gly, Val, Ala, and Pro, which are often present in repeats of tetra-, penta-, and hexapeptides, such as Gly-Gly-Val-Pro, Gly-Val-Gly-Val-Pro, Gly-Val-Pro-Gly-Val, and Gly-Val-Gly-Val-Ala-Pro, respectively [3, 4]. The hydrophilic domains are mainly composed of lysines interspersed by alanines. 

Miao M, Cirulis JT, Lee S et al (2005) Structural determinants of cross- linking and hydrophobic domains for self-assembly of elastin-like polypeptides. Biochemistry 44 14367-14375... 

The process of coacervation is finely tuned to the physiological conditions of the extracellular matrix. Optimal coacervation of human tropo-elastin occurs at 37 °G, 150 mM NaCl, and pH 7-8 (Vrhovski et al, 1997). The arrangement of sequences in tropoelastin is critical to this process of coacervation, where association through hydrophobic domains depends on their contextual location in the molecule (Toonkool et al., 2001b). Tropoelastin association rapidly proceeds through a monomer to tuner transition, with little evidence of intermediate forms (Toonkool et al, 2001a). 

The protein elastin presents another opportunity to create amyloid-like fibrils from natural proteins for the purpose of developing biomaterials. Elastin is found in tissue where it imparts elastic recoil, and fibrils formed from this protein may demonstrate some of the elastic properties of the constituent elastic proteins (Bochicchio et al., 2007). Elastin typically contains the sequence poly(ZaaGlyGlyYaaGly) (where Zaa, Yaa = Val or Leu) (Tamburro et al., 2005), and short stretches of the protein retain the ability to form structures similar to the original protein. Simple proline to glycine mutations in the hydrophobic domains of elastin can induce the formation of amyloid-like fibrils (Miao et al., 2003), suggesting that fibrillar materials can be easily generated from these sequences. 

The hydrophobic domain of elastin is a compact, dynamic structure which forms shortlived interconverting structures distorted (3 strands, fluctuating (3 turns, and buried hydro-phobic residues. Nevertheless, the numerous amide groups in the peptide bonds can still hydrogen bond with water. The overall structure is therefore a compact amorphous... 

Hydrophilic cross-linking exons Hydrophobic exons Fig. 49.6. The cDNA structure of elastin, indicating the repeating cross-linking and hydrophobic domains. 

The precise understanding of the structural nature of elastin remains elusive because the unusual physical properties of native elastin have prevented the use of traditional structural biology techniques. The hydrophobic domains are dominated by a pentapeptide repeat sequence of (Val-Pro-Gly-Val-Gly). This repeat sequence is believed to endow elastin its remarkable elastic properties, allowing continual expansion and contractions without loss of structural integrity (2). 

Another type of inportant structural ECM proteins, the elastin, is rich in elastic tissues and organs, such as the cardiovascular and pulmonary system and skin, and of extreme importance for their proper function. The precursors of native elastin, the tropoelastins, are composed of alternating hydrophobic domains, enabling hydrophobic interaction, and lysine-rich domains, allowing for covalent cross-linking through the mediation of the enzyme lysyl oxidase. 

Elastin-like polypeptides are polymers that consist of alternating hydrophobic blocks and crosslinking domains. Such polymers can be produced recombinantly and are composed of the repeating amino acid sequence (Val-Pro-Gly-Xaa-Gly)m, where Xaa is a hydrophobic domain that facilitates both self-aggregation and elastomeric functions. Thus, they undergo an inverse phase transition, which can be used to promote temperature-dependent self-assembly [125]. 

Fig. 6.6 Elastic fiber structure. Elastin is cross-linked at the KA and KP domains. The remainder of the molecule is hydro-phobic. When stretched these hydrophobic regions come into excessive contact with the water and return to a more globular structure on relaxation (Adapted from Fig.19-52 in The Molecular Biology of the Cell. B. Alberts et ah, 4th Ed. 2002, Garland Science, Taylor Francis Group, New York)...

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