2021
DOI: 10.1371/journal.pcbi.1009079
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Mechanism of collagen folding propagation studied by Molecular Dynamics simulations

Abstract: Collagen forms a characteristic triple helical structure and plays a central role for stabilizing the extra-cellular matrix. After a C-terminal nucleus formation folding proceeds to form long triple-helical fibers. The molecular details of triple helix folding process is of central importance for an understanding of several human diseases associated with misfolded or unstable collagen fibrils. However, the folding propagation is too rapid to be studied by experimental high resolution techniques. We employed mu… Show more

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Cited by 13 publications
(15 citation statements)
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“…It is well-known that genetic defects in the collagen type I genes COL1A1 and COL1A2 can cause osteogenesis imperfecta, Caffey disease and Ehlers–Danlos syndrome with a distinct bone or skin pathology, but our limited knowledge of the collagen folding hierarchy and its tissue-specific interfering factors makes it difficult to understand the mechanisms leading to such hyperostosis or fragility of bones, skin or blood vessels ( 81 83 ). The results presented here show that collagen hydration modulates the assembly rate and diameter of fibrils, properties that are also impacted in these diseases ( 84 86 ). It is therefore not unlikely that modified hydration may exacerbate the molecular defects of collagen Type I (i.e., excessive posttranslational modification, misfolding) in determining the phenotypic outcome.…”
Section: Discussionmentioning
confidence: 71%
“…It is well-known that genetic defects in the collagen type I genes COL1A1 and COL1A2 can cause osteogenesis imperfecta, Caffey disease and Ehlers–Danlos syndrome with a distinct bone or skin pathology, but our limited knowledge of the collagen folding hierarchy and its tissue-specific interfering factors makes it difficult to understand the mechanisms leading to such hyperostosis or fragility of bones, skin or blood vessels ( 81 83 ). The results presented here show that collagen hydration modulates the assembly rate and diameter of fibrils, properties that are also impacted in these diseases ( 84 86 ). It is therefore not unlikely that modified hydration may exacerbate the molecular defects of collagen Type I (i.e., excessive posttranslational modification, misfolding) in determining the phenotypic outcome.…”
Section: Discussionmentioning
confidence: 71%
“…For example, monomeric globular proteins can fold in a millisecond to second timescale, while larger multihelical fibrous proteins such as collagen can take from minutes to hours to fold (Baum and Brodsky, 1997). Mutations in the protein may increase the folding time (Hartmann and Zacharias, 2021).…”
Section: Downloaded Frommentioning
confidence: 99%
“…To tackle this challenge, information is gained from computer simulations, as well as from experimental techniques targeted to interfacial regions. During the past decades, theoretical modeling has become a well established tool to investigate the morphology of complex systems. , Simulations provide three-dimensional real-time imaging of systems with atomistic-level resolution and so essential structural and dynamical information that are hardly accessible by any experimental method . Also, following the developments in hardware and software, simulations of large structures are possible and can now serve as a molecular microscope. , On the experimental side, second harmonic generation (SHG), which is based on a nonlinear optical (NLO) process, is particularly relevant to study membranes because the response is sensitive to the symmetry of the molecular assemblies and requires noncentrosymmetry.…”
Section: Introductionmentioning
confidence: 99%