Allysine modifications perturb tropoelastin structure and mobility on a local and global scale.

Elastin provides elastic tissues with resilience through stretch and recoil cycles, and is primarily made of its extensively cross-linked monomer, 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. We used replica exchange molecular dynamics to generate structural ensembles of allysine containing tropoelastin. We conducted principal component analysis on these ensembles and found that the molecule departs from the canonical structural ensemble. 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. Additionally, we highlighted secondary structural changes and linked these perturbations to the longevity of specific salt bridges. We propose a model where allysines in tropoelastin contribute to hierarchical elastin assembly through global and local perturbations to molecular structure and dynamics.

Pubmed ID: 33543005