Tropoelastin bridge region positions the cell-interactive C terminus and contributes to elastic fiber assembly

Giselle C Yeo, Clair Baldock, Anne Tuukkanen, Manfred Roessle, Leanne B Dyksterhuis, Steven G Wise, Jacqueline Mary Matthews, Suzanne M Mithieux, Anthony S Weiss

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35 Citations (Scopus)

Abstract

The tropoelastin monomer undergoes stages of association by coacervation, deposition onto microfibrils, and cross-linking to form elastic fibers. Tropoelastin consists of an elastic N-terminal coil region and a cell-interactive C-terminal foot region linked together by a highly exposed bridge region. The bridge region is conveniently positioned to modulate elastic fiber assembly through association by coacervation and its proximity to dominant cross-linking domains. Tropoelastin constructs that either modify or remove the entire bridge and downstream regions were assessed for elastogenesis. These constructs focused on a single alanine substitution (R515A) and a truncation (M155n) at the highly conserved arginine 515 site that borders the bridge. Each form displayed less efficient coacervation, impaired hydrogel formation, and decreased dermal fibroblast attachment compared to wild-type tropoelastin. The R515A mutant protein additionally showed reduced elastic fiber formation upon addition to human retinal pigmented epithelium cells and dermal fibroblasts. The small-angle X-ray scattering nanostructure of the R515A mutant protein revealed greater conformational flexibility around the bridge and C-terminal regions. This increased flexibility of the R515A mutant suggests that the tropoelastin R515 residue stabilizes the structure of the bridge region, which is critical for elastic fiber assembly.
Original languageEnglish
Pages (from-to)2878 - 2883
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number8
DOIs
Publication statusPublished - 2012

Cite this

Yeo, G. C., Baldock, C., Tuukkanen, A., Roessle, M., Dyksterhuis, L. B., Wise, S. G., Matthews, J. M., Mithieux, S. M., & Weiss, A. S. (2012). Tropoelastin bridge region positions the cell-interactive C terminus and contributes to elastic fiber assembly. Proceedings of the National Academy of Sciences of the United States of America, 109(8), 2878 - 2883. https://doi.org/10.1073/pnas.1111615108