Designing collagens to shed light on the multi-scale structure-function mapping of matrix disorders.

Autor: Gahlawat S; Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA., Nanda V; Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.; Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, NJ, USA., Shreiber DI; Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Jazyk: angličtina
Zdroj: Matrix biology plus [Matrix Biol Plus] 2023 Dec 14; Vol. 21, pp. 100139. Date of Electronic Publication: 2023 Dec 14 (Print Publication: 2024).
DOI: 10.1016/j.mbplus.2023.100139
Abstrakt: Collagens are the most abundant structural proteins in the extracellular matrix of animals and play crucial roles in maintaining the structural integrity and mechanical properties of tissues and organs while mediating important biological processes. Fibrillar collagens have a unique triple helix structure with a characteristic repeating sequence of (Gly-X-Y) n . Variations within the repetitive sequence can cause misfolding of the triple helix, resulting in heritable connective tissue disorders. The most common variations are single-point missense mutations that lead to the substitution of a glycine residue with a bulkier amino acid (Gly → X). In this review, we will first discuss the importance of collagen's triple helix structure and how single Gly substitutions can impact its folding, structure, secretion, assembly into higher-order structures, and biological functions. We will review the role of "designer collagens," i.e., synthetic collagen-mimetic peptides and recombinant bacterial collagen as model systems to include Gly → X substitutions observed in collagen disorders and investigate their impact on structure and function utilizing in vitro studies. Lastly, we will explore how computational modeling of collagen peptides, especially molecular and steered molecular dynamics, has been instrumental in probing the effects of Gly substitutions on structure, receptor binding, and mechanical stability across multiple length scales.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2023 The Authors.)
Databáze: MEDLINE
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