![]() ![]() Thus, it is probable that the presence of allysines can also affect the conformation of tropoelastin, and in turn, influence coacervation and subsequent higher order assembly processes. The delicate balance between molecular arrangement and function can be perturbed by mutations that result in structural changes within both tropoelastin molecules and elastin fibers. 1), both of which are dependent on its molecular arrangement and flexibility, ,, , ]. Elastin assembly is a finely tuned process relying on the intrinsic properties of tropoelastin, including the association of its hydrophobic domains and positioning of its cross-linking domains ( Fig. The contribution of allysines to elastin assembly, other than purely their ability to form cross-links, is currently unknown. These four types of links are the most abundant cross-linked species within the mature elastin fiber. LNL and ALL are able to condense further, forming larger, more complex cross-links such as desmosine or isodesmosine. Allysines are capable of undergoing spontaneous condensation with either the ε-amino groups of lysines or the semialdehydes of other allysines, forming linear lysinonorleucine (LNL) or allysine-aldol (ALL) cross-links respectively. As an amine oxidase, LOX modifies the ε-amino side chain of lysine to an α-aminoadipic δ-semialdehyde, resulting in an allysine residue. The cross-linking of elastin is facilitated by one or more members of the family of lysyl oxidase (LOX) enzymes and commences prior to deposition onto the microfibrillar scaffold. These spherules are then deposited onto the microfibrillar scaffold within the ECM where they assemble into robust, insoluble, and extensively cross-linked fibers. Assembly is initiated after secretion to the cell surface, where tropoelastin molecules rapidly form small spherules through a process termed coacervation. The elastin polymer predominantly comprises its soluble subunit, tropoelastin, which is secreted by elastogenic cells and undergoes hierarchical self-assembly to form elastin fibers. We propose a model where allysines in tropoelastin contribute to hierarchical elastin assembly through global and local perturbations to molecular structure and dynamics.Įlastin is the major elastic extracellular matrix (ECM) protein that is crucial for the mechanical resilience of elastic vertebrate tissues, including the skin, lungs and cardiovascular system. Additionally, we highlighted secondary structural changes and linked these perturbations to the longevity of specific salt bridges. Furthermore, we showed that, while the canonical scissors-twist movement was retained, new movements emerged that deviated from those of the wild type protein, providing evidence for the involvement of a variety of molecular motions in elastin assembly. We conducted principal component analysis on these ensembles and found that the molecule departs from the canonical structural ensemble. We used replica exchange molecular dynamics to generate structural ensembles of allysine containing tropoelastin. Here, we leverage the recently published full atomistic model of tropoelastin to assess how allysine modifications, which are essential to cross-linking, contribute to the dynamics and structural changes that occur in tropoelastin in the context of elastin assembly. ![]() Elastin provides elastic tissues with resilience through stretch and recoil cycles, and is primarily made of its extensively cross-linked monomer, tropoelastin. ![]()
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