Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 3, Issue 11, Pages 2832-2844Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.6b00564
Keywords
tropoelastin; glutamate; hinge region; small-angle X-ray scattering; solution structure
Categories
Funding
- Australian Research Council [DP120103911, DP130103693]
- National Health & Medical Research Council [APP1075357]
- Biotechnology and Biological Sciences Research Council [BB/L00612X/1]
- Wellcome Trust [088785/Z/09/Z]
- Biotechnology and Biological Sciences Research Council [BB/L00612X/1] Funding Source: researchfish
- BBSRC [BB/L00612X/1] Funding Source: UKRI
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Tropoelastin, as the monomer unit of elastin, assembles into elastic fibers that impart strength and resilience to elastic tissues. Tropoelastin is also widely used to manufacture versatile materials with specific mechanical and biological properties. The assembly of tropoelastin into elastic fibers or biomaterials is crucially influenced by key submolecular regions and specific residues within these domains. In this work, we identify the functional contributions of two rarely occurring negatively charged residues, glutamate 345 in domain 19 and glutamate 414 in domain 21, in jointly maintaining the native conformation of the tropoelastin hinge, bridge and foot regions. Alanine substitution of E345 and/or E414 variably alters the positioning and interactive accessibility of these regions, as illustrated by nanostructural studies and detected by antibody and cell probes. These structural changes are associated with a lower propensity for monomer coacervation, cross-linking into morphologically and functionally atypical hydrogels, and markedly impaired and abnormal elastic fiber formation. Our work indicates the crucial significance of both E345 and E414 residues in modulating specific local structure and higher-order assembly of human tropoelastin.
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