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
Giselle C YeoAnthony S Weiss

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...Continue Reading

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Citations

Aug 22, 2013·Expert Reviews in Molecular Medicine·Andrew K BaldwinCay M Kielty
Aug 14, 2013·Acta Biomaterialia·Steven G WiseAnthony S Weiss
Jul 13, 2012·Advanced Drug Delivery Reviews·Suzanne M MithieuxAnthony S Weiss
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Feb 10, 2016·Tissue Engineering. Part a·Steven G WiseAnthony Weiss
Jan 21, 2015·Matrix Biology : Journal of the International Society for Matrix Biology·Steven R Van Doren
Oct 11, 2017·Journal of Physics D: Applied Physics·Yanhang ZhangGregory S Boutis
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Jun 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Anna TarakanovaMarkus J Buehler
Oct 25, 2014·The Journal of Biological Chemistry·Giselle C YeoAnthony S Weiss
Jun 30, 2019·Matrix Biology : Journal of the International Society for Matrix Biology·Sean E ReichheldFred W Keeley
Dec 17, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Manuel Gomez-FloritManuela E Gomes
Mar 16, 2021·Frontiers in Bioengineering and Biotechnology·Jazmin OzsvarAnthony S Weiss
Apr 26, 2021·The FEBS Journal·Christian E H Schmelzer, Laurent Duca
Aug 7, 2021·Matrix Biology Plus·Mukti SinghClair Baldock
Nov 21, 2017·ACS Biomaterials Science & Engineering·Giselle C YeoAnthony S Weiss

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