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Matrix Biol. 2019 Jun 26. pii: S0945-053X(19)30160-X. doi: 10.1016/j.matbio.2019.06.010. [Epub ahead of print]

Sequence variants of human tropoelastin affecting assembly, structural characteristics and functional properties of polymeric elastin in health and disease.

Author information

1
Molecular Medicine Program, Research Institute, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G0A4, Canada.
2
Department of Biochemistry, University of Toronto, 1 King's College Circle, Medical Sciences Building, Toronto, ON M5S1A8, Canada.
3
Molecular Medicine Program, Research Institute, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G0A4, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Medical Sciences Building, Toronto, ON M5S1A8, Canada.
4
Molecular Medicine Program, Research Institute, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G0A4, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Medical Sciences Building, Toronto, ON M5S1A8, Canada. Electronic address: fwk@sickkids.ca.

Abstract

Elastin is the polymeric protein responsible for the physiologically important properties of extensibility and elastic recoil of cardiovascular, pulmonary and many other tissues. In spite of significant advances in the understanding how monomeric tropoelastin is assembled into the polymeric elastic matrix, details of this assembly process are still lacking. In particular it is not clear how the various architectures and more subtle elastic properties required by diverse elastic tissues can arise from the protein product of a single gene. While monomeric tropoelastin has the intrinsic ability to self-assemble into fibrillar structures, it is clear that in vivo assembly is guided by interactions with cells and other matrix-associated components. In addition, the multiplicity of reported mRNA isoforms of human tropoelastin, if translated into protein variants, could modulate not only interactions with these matrix-associated components but also self-assembly and functional properties. Critical information identifying such protein isoforms of human tropoelastin is only now emerging from mass spectrometric studies. Increased levels of complexity of the assembly process provide additional opportunities for production of polymeric elastins with aberrant architectures and sub-optimal functional properties that could affect the longer-term structural integrity of elastic matrices. Biophysical techniques, such as SAXS, NMR and molecular dynamics, have provided a means to discern details of the effects of sequence variants, including both alternate splicing isoforms and genetic polymorphisms, on the dynamic flexibility of elastin required for its elastomeric properties. Such approaches promise to provide important new insights into the relationship between sequence, structural characteristics, assembly and functional properties of elastin in both health and disease.

KEYWORDS:

Durability of elastic matrices; Matrix assembly and architecture; Single nucleotide polymorphisms; Splice variants; Tropoelastin

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