Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly
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e1501145.full.pdf
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Author(s)
Yeo, Giselle C.
Tarakanova, Anna
Baldock, Clair
Wise, Steven G.
Weiss, Anthony S.
Buehler, Markus J
Date Issued
February 2016
Journal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Yeo, Giselle C., Anna Tarakanova, Clair Baldock, Steven G. Wise, Markus J. Buehler, and Anthony S. Weiss. "Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly." Science Advances 2.2 (February 2016): e1501145.
Version
Final published version
Abstract
The assembly of the tropoelastin monomer into elastin is vital for conferring elasticity on blood vessels, skin, and lungs. Tropoelastin has dual needs for flexibility and structure in self-assembly. We explore the structure-dynamics-function interplay, consider the duality of molecular order and disorder, and identify equally significant functional contributions by local and global structures. To study these organizational stratifications, we perturb a key hinge region by expressing an exon that is universally spliced out in human tropoelastins. We find a herniated nanostructure with a displaced C terminus and explain by molecular modeling that flexible helices are replaced with substantial β sheets. We see atypical higher-order cross-linking and inefficient assembly into discontinuous, thick elastic fibers. We explain this dysfunction by correlating local and global structural effects with changes in the molecule’s assembly dynamics. This work has general implications for our understanding of elastomeric proteins, which balance disordered regions with defined structural modules at multiple scales for functional assembly.
MIT Department
Massachusetts Institute of Technology. Department of Civil and Environmental Engineering
Massachusetts Institute of Technology. Laboratory for Atomistic and Molecular Mechanics
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1126/sciadv.1501145
