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 crosslinked to make elastin, Assembly by coace rvation was examined for an isoform of tropoelastin that lacks the hydrophi lic domain encoded by exon 26A It is equivalent to a naturally secreted for m 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 pr oteins were examined for their ability to interact with extracellular matri x glycosaminoglycans. These negatively charged molecules interacted with po sitively 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 depo sition during elastogenesis is encouraged by local exposure to matrix glyco saminoglycans. Unmodified proteins are retained at similar to 3 mu M dissoc iation constant. Following lysyl oxidase modification of tropoelastin lysin e residues, they are released from glycosaminoglycan interactions, thereby permitting those residues to contribute to elastin cross-links.