Abstract
The protein elastin imparts extensibility, elastic recoil, and resilience to tissues including arterial walls, skin, lung alveoli, and the uterus. Elastin and elastin-like peptides are hydrophobic, disordered, and undergo liquid-liquid phase separation upon self-assembly. Despite extensive study, the structure of elastin remains controversial. We use molecular dynamics simulations on a massive scale to elucidate the structural ensemble of aggregated elastin-like peptides. Consistent with the entropic nature of elastic recoil, the aggregated state is stabilized by the hydrophobic effect. However, self-assembly does not entail formation of a hydrophobic core. The polypeptide backbone forms transient, sparse hydrogen-bonded turns and remains significantly hydrated even as self-assembly triples the extent of non-polar side chain contacts. Individual chains in the assembly approach a maximally-disordered, melt-like state which may be called the liquid state of proteins. These findings resolve long-standing controversies regarding elastin structure and function and afford insight into the phase separation of disordered proteins.
Highlights
The elasticity of skin, lungs, major arteries, and other vertebrate tissues is imparted by elastin, a modular structural protein composed of alternating hydrophobic and cross-linking domains.[1]
Deviation from ideality reflects the finite size of the aggregate, finite chain length, the presence of local secondary structure (Fig. 2c), and persistent hydration (Fig. 3, Fig. S9). These results suggest that elastin—and polypeptide chains in general—cannot make polymer melts in the idealized, solvent-excluding sense because backbone groups must form hydrogen bonds either with each other, which leads to ordering, or with water molecules, whose presence is required for disorder
In spite of its moderate size, this molecular system emulates a biphasic liquid in which both phases have attained a state of higher entropy than in the mixed system: the higher entropy of the aqueous phase results from the hydrophobic effect, which is manifested by a three-fold increase in burial of non-polar groups for each polypeptide chain in the aggregate compared to the monomeric form
Summary
The elasticity of skin, lungs, major arteries, and other vertebrate tissues is imparted by elastin, a modular structural protein composed of alternating hydrophobic and cross-linking domains.[1]. Numerous structural models of elastin have been proposed, which span a range from highly-ordered[6] to maximally-disordered[7,8] and emphasize either the hydrophobic effect[6,9,10,11] or conformational entropy[7,8,12] as the dominant contribution to the elastic recoil force.
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