Glycosaminoglycans mediate the coacervation of human tropoelastin through dominant charge interactions involving lysine side chains.
Following cellular secretion into the extracellular matrix, tropoelastin is transported, deposited, and cross-linked to make elastin. Assembly by coacervation was examined for an isoform of tropoelastin that lacks the hydrophilic domain encoded by exon 26A. It is equivalent to a naturally secreted form of tropoelastin and shows similar coacervation performance to its partner containing 26A, thereby generalizing the concept that splice form variants are able to coacervate under comparable conditions. This is optimal under physiological conditions of temperature, salt concentration, and pH. The proteins were examined for their ability to interact with extracellular matrix glycosaminoglycans. These negatively charged molecules interacted with positively charged lysine residues and promoted coacervation of tropoelastin in a temperature- and concentration-dependent manner. A testable model for elastin-glycosaminoglycan interactions is proposed, where tropoelastin deposition during elastogenesis is encouraged by local exposure to matrix glycosaminoglycans. Unmodified proteins are retained at approximately 3 microM dissociation constant. Following lysyl oxidase modification of tropoelastin lysine residues, they are released from glycosaminoglycan interactions, thereby permitting those residues to contribute to elastin cross-links.
Department of Biochemistry, University of Sydney, Sydney, NSW 2006, Australia.
W J
WJ
Wu
B
B
Vrhovski
A S
AS
Weiss
D005091:Exons; D006025:Glycosaminoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008239:Lysine; D016297:Mutagenesis, Site-Directed; D009994:Osmolar Concentration; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D013816:Thermodynamics; D014333:Tropoelastin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D006025:Glycosaminoglycans; D020033:Protein Isoforms; D011994:Recombinant Proteins; D014333:Tropoelastin; D006493:Heparin; D008239:Lysine