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

• Main Authors: Tarakanova, Anna (Author), Buehler, Markus J (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Civil and Environmental Engineering (Contributor)
• Format: Article
• Language: English
• Published: Elsevier BV, 2020-06-04T17:43:19Z.
• Subjects: Article
• Online Access: Get fulltext

Elastin provides elastic tissues with resilience through stretch and recoil cycles, and is primarily made of itsextensively cross-linked monomer, tropoelastin. Here, we leverage the recently published full atomistic modelof tropoelastin to assess how allysine modifications, which are essential to cross-linking, contribute to thedynamics and structural changes that occur in tropoelastin in the context of elastin assembly. We used replicaexchange molecular dynamics to generate structural ensembles of allysine containing tropoelastin. Weconducted principal component analysis on these ensembles and found that the molecule departs from thecanonical structural ensemble. Furthermore, we showed that, while the canonical scissors-twist movementwas retained, new movements emerged that deviated from those of the wild type protein, providing evidencefor 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. Wepropose a model where allysines in tropoelastin contribute to hierarchical elastin assembly through global andlocal perturbations to molecular structure and dynamics.
National Science Foundation (U.S.) (Grant ACI-1053575)
United States. Office of Naval Research. Defense University Research Instrumentation Program (Grant N00014-17-1-2320)
United States. Office of Naval Research (Grant N000141612333)
National Institutes of Health (U.S.) (Grant 5U01EB014976)