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Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly.


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 ? 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.

SUBMITTER: Yeo GC 

PROVIDER: S-EPMC4795673 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly.

Yeo Giselle C GC   Tarakanova Anna A   Baldock Clair C   Wise Steven G SG   Buehler Markus J MJ   Weiss Anthony S AS  

Science advances 20160205 2


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 tha  ...[more]

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