Tropoelastin bridge region positions the cell-interactive C terminus and contributes to elastic fiber assembly
| Autor: | Manfred Roessle, Steven G. Wise, Anne Tuukkanen, Clair Baldock, Giselle C. Yeo, Jacqueline M. Matthews, Leanne B Dyksterhuis, Anthony S. Weiss, Suzanne M. Mithieux |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular metabolism [Elastic Tissue] Materials science Flexibility (anatomy) Mutant Elastic fiber assembly Cell Communication metabolism [Tropoelastin] Dermal fibroblast Structure-Activity Relationship Mutant protein Tropoelastin medicine Cell Adhesion Humans metabolism [Mutant Proteins] Particle Size Cells Cultured Multidisciplinary Microscopy Confocal biology integumentary system C-terminus Temperature chemistry [Elastic Tissue] Hydrogels Fibroblasts Biological Sciences Elastic Tissue ultrastructure [Tropoelastin] Protein Structure Tertiary Solutions medicine.anatomical_structure Biochemistry chemistry [Mutant Proteins] chemistry [Tropoelastin] Proteolysis biology.protein Biophysics ddc:000 ultrastructure [Elastic Tissue] Mutant Proteins pathology [Fibroblasts] Elastic fiber metabolism [Fibroblasts] |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America 109, 2878-2883 (2012). doi:10.1073/pnas.1111615108 |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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