Dr. Sarah Rauscher - June 10

The Liquid Structure of Elastin

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 structurally-disordered, hydrophobic proteins that undergo liquid-liquid phase separation upon increasing temperature. Despite extensive study for over eighty years, the structure of elastin, the protein responsible for tissue elasticity,remains controversial. Various idealized models ranging from maximally-disordered to highly-ordered were proposed based on different sets of experimental data. Using molecular dynamics (MD) simulations, we have obtained an unprecedented atomistic view of the structural ensemble of an elastin-like aggregate. The elastin aggregate is found to consist of highly disordered chains that retain local secondary structure in the form of hydrogen-bonded turns. Our findings defy conventional wisdom about protein folding and disorder: (1) although the peptide side-chains are hydrophobic, they do not form a hydrophobic core; (2) although the polypeptide backbone forms hydrogen-bonded turns, it remains significantly hydrated; and (3) although the structure of elastin aggregates is nearly maximally disordered, it is not random. The fact that polypeptide chains can aggregate yet retain functionally-essential conformational entropy is of broad relevance to the study of both protein disorder and protein phase separation: the structural ensemble of the elastin-like aggregate provides the first ;atomistic view into what may be described as the liquid state of proteins.

 

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