Transglutaminase-Mediated Cross-Linking of Tropoelastin to Fibrillin Stabilises the Elastin Precursor Prior to Elastic Fibre Assembly

Autor: Helena Newandee, Anthony S. Weiss, Clair Baldock, Jennifer Thomson, Michael P. Lockhart-Cairns, Anna Tarakanova
Rok vydání: 2020
Předmět:
Models
Molecular
TG2
transglutaminase-2
Protein Conformation
Tissue transglutaminase
Fibrillin-1
elastin
fibrillin
tissue transglutaminase
macromolecular substances
Article
RMSF
root mean square fluctuation
03 medical and health sciences
0302 clinical medicine
GTP-Binding Proteins
Tropoelastin
Structural Biology
REMD
Replica Exchange molecular dynamics
Humans
Protein Glutamine gamma Glutamyltransferase 2
TE
tropoelastin
Molecular Biology
030304 developmental biology
EGF
epidermal growth factor
0303 health sciences
AUC
analytical ultracentrifugation
Transglutaminases
integumentary system
biology
Small-angle X-ray scattering
Chemistry
Elastic fibre assembly
SAXS
small-angle X-ray scattering
elastic fibres
MALS
multi-angle light scattering
Elastic fibres
HEK293 Cells
biology.protein
Biophysics
SEC
size exclusion chromatography
Microfibril
Fibrillin
Elastin
030217 neurology & neurosurgery
TB
TGFβ binding-like
Zdroj: 'Journal of Molecular Biology ', vol: 432, pages: 5736-5751 (2020)
Journal of Molecular Biology
ISSN: 0022-2836
Popis: Elastic fibres are essential components of all mammalian elastic tissues such as blood vessels, lung and skin, and are critically important for the mechanical properties they endow. The main components of elastic fibres are elastin and fibrillin, where correct formation of elastic fibres requires a fibrillin microfibril scaffold for the deposition of elastin. It has been demonstrated previously that the interaction between fibrillin and tropoelastin, the elastin precursor, increases the rate of assembly of tropoelastin. Furthermore, tropoelastin and fibrillin can be cross-linked by transglutaminase-2, but the function of cross-linking on their elastic properties is yet to be elucidated. Here we show that transglutaminase cross-linking supports formation of a 1:1 stoichiometric fibrillin–tropoelastin complex. SAXS data show that the complex retains features of the individual proteins but is elongated supporting end-to-end assembly. Elastic network models were constructed to compare the dynamics of tropoelastin and fibrillin individually as well as in the cross-linked complex. Normal mode analysis was performed to determine the structures' most energetically favourable, biologically accessible motions which show that within the complex, tropoelastin is less mobile and this molecular stabilisation extends along the length of the tropoelastin molecule to regions remote from the cross-linking site. Together, these data suggest a long-range stabilising effect of cross-linking that occurs due to the covalent linkage of fibrillin to tropoelastin. This work provides insight into the interactions of tropoelastin and fibrillin and how cross-link formation stabilises the elastin precursor so it is primed for elastic fibre assembly.
Graphical abstract Unlabelled Image
Highlights • Elastic fibres, essential for mammalian tissue elasticity, contain elastin and fibrillin. • Tissue transglutaminase cross-links fibrillin and tropoelastin to form a complex. • The complex has an elongated structure that supports end-to-end assembly. • Cross-linking restricts the molecular motions of tropoelastin and fibrillin. • Stabilisation may provide an initiating molecular mechanism for elastic fibre assembly.
Databáze: OpenAIRE
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