Towards a Better Understanding of the Influence of Carbohydrates on the Structural, Dynamic, and Functional Properties of Fibromodulin: Crucial Insights From a Comparative In Silico Approach DOI Creative Commons
Rajas Rao, Manuel Dauchez, Stéphanie Baud

et al.

Proteoglycan Research, Journal Year: 2024, Volume and Issue: 2(4)

Published: Oct. 1, 2024

ABSTRACT Proteoglycans are a class of biological macromolecules that characterized by the presence long chains negatively charged glycosaminoglycans (GAGs). One family proteoglycans, small leucine‐rich proteoglycans (SLRPs), is well‐conserved proteins, which predominantly present in extracellular matrix and critical components numerous processes matrix. Interestingly, fibromodulin (FMOD), one members SLRP exists both as proteoglycan glycoprotein juveniles old‐aged individuals, respectively. Despite their physiological significance interesting variations carbohydrate composition, structural dynamics (e.g., evolution structure over time), 3D conformational preferences remains unexplored to date. In this study, molecular modeling techniques were used investigate effects changes composition on dynamics. A total 6µs all‐atom simulations performed three types systems: non‐glycosylated FMOD, form lacking keratan sulfate disaccharides with GAGs. Substantial found FMOD between states. These accompanied modifications curved‐solenoid architecture well local solvent accessibilities some residues. relatively rigid, motif, sequence across various species, was identified unstructured N‐terminal domain. This motif highly accessible states, despite its proximity chains. two features (rigididy high accessibility) suggest key role for protein‐protein interactions established Fibromodulin. Overall, study provides insight into how influences protein functions.

Language: Английский

Role of TMEM230 in the Aberrant Glycosylation in Human Autoimmunity and Cancer DOI Creative Commons
Elena Angeli, Cinzia Cocola, Edoardo Abeni

et al.

Proteoglycan Research, Journal Year: 2025, Volume and Issue: 3(1)

Published: Jan. 1, 2025

ABSTRACT Alterations in glycoconjugate profiles are thought to promote changes cell‐to‐cell and cell‐to‐intracellular extracellular scaffold interactions human disease. The nearly unlimited number of “glycoforms” that may exist nature difficult study due glycosylation modifications being associated with non‐genome coded posttranscription post‐translation processes. Specific products generated by dependent on concentration sub‐cellular locations glycan synthesis processing enzymes. An indirect “high‐throughput” approach is characterize enzymes (hydrolases transferases) single cell sequencing all types tissue diseases. We previously identified TMEM230 as an endoplasmic reticulum (ER) protein regulates NOTCH glycoprotein receptor ligand signaling zebrafish blood vessel formation destructive remodeling capacities diverse including fibroblast, phagocytic immune system cells patients cancer or granulomatous systemic vasculitis autoimmune disorder. represents a paradigm mediated signal transduction supports the role modifications. ER initiates earliest steps synthesis, sorting, trafficking. As remodeling, Notch hallmarks disorders, we investigated whether aberrant expression was also rheumatoid arthritis (RA). In this current study, analysis supported downregulated synovial RA while were predominantly upregulated. contrast, upregulated high‐grade compared low‐grade gliomas it N‐linked (GlcNAc), glycosaminoglycan expression. Our collective results support glycan/glycoconjugate aggressive gliomas. therefore be therapeutic target marker for clinical treatment induced autoimmunity disorders cancer.

Language: Английский

Citations

1

Comprehensive Investigation of Proteoglycan Gene Expression in Breast Cancer: Discovery of a Unique Proteoglycan Gene Signature Linked to the Malignant Phenotype DOI Creative Commons
Simone Buraschi, Gabriel J. Pascal, Federico Liberatore

et al.

Proteoglycan Research, Journal Year: 2025, Volume and Issue: 3(1)

Published: Jan. 1, 2025

Solid tumors present a formidable challenge in oncology, necessitating innovative approaches to improve therapeutic outcomes. Proteoglycans, multifaceted molecules within the tumor microenvironment, have garnered attention due their diverse roles cancer progression. Their unique ability interact with specific membrane receptors, growth factors, and cytokines provides promising avenue for development of recombinant proteoglycan-based therapies that could enhance precision efficacy treatment. In this study, we performed comprehensive analysis proteoglycan gene landscape human breast carcinomas. Leveraging available wealth genomic clinical data regarding expression carcinoma using machine learning model, identified signature composed five proteoglycans differentially modulated tissue: Syndecan-1 asporin (upregulated) decorin, PRELP podocan (downregulated). Additional query revealed serglycin, previously shown be increased patients mouse models correlate poor prognosis, was indeed decreased vast majority its levels inversely correlated progression invasion. This provide novel diagnostic capabilities biology highlights need further utilization publicly datasets validation preclinical experimental results.

Language: Английский

Citations

0

Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling DOI Creative Commons
Marsioleda Kemberi, Alexander Frederick Minns, Salvatore Santamaria

et al.

Proteoglycan Research, Journal Year: 2024, Volume and Issue: 2(4)

Published: Oct. 1, 2024

Proteoglycans and their proteolytic fragments diffuse into biological fluids such as plasma, serum, urine, or synovial fluid, where they can be detected by antibodies mass-spectrometry. Neopeptides generated the proteolysis of proteoglycans are recognized specific neoepitope act a proxy for activity certain proteases. Proteoglycan proteoglycan potentially used prognostic, diagnostic, theragnostic biomarkers several diseases characterized dysregulated extracellular matrix remodeling osteoarthritis, rheumatoid arthritis, atherosclerosis, thoracic aortic aneurysms, central nervous system disorders, viral infections, cancer. Here, we review main mechanisms accounting presence soluble in fluids, potential application biomarkers, highlight challenges opportunities ahead clinical translation.

Language: Английский

Citations

2

Proteomic Profiling of Endothelial Cell Secretomes After Exposure to Calciprotein Particles Reveals Downregulation of Basement Membrane Assembly and Increased Release of Soluble CD59 DOI Open Access
Alexander D. Stepanov, Д. К. Шишкова, Victoria Markova

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11382 - 11382

Published: Oct. 23, 2024

Calciprotein particles (CPPs) are essential circulating scavengers of excessive Ca

Language: Английский

Citations

1

Towards a Better Understanding of the Influence of Carbohydrates on the Structural, Dynamic, and Functional Properties of Fibromodulin: Crucial Insights From a Comparative In Silico Approach DOI Creative Commons
Rajas Rao, Manuel Dauchez, Stéphanie Baud

et al.

Proteoglycan Research, Journal Year: 2024, Volume and Issue: 2(4)

Published: Oct. 1, 2024

ABSTRACT Proteoglycans are a class of biological macromolecules that characterized by the presence long chains negatively charged glycosaminoglycans (GAGs). One family proteoglycans, small leucine‐rich proteoglycans (SLRPs), is well‐conserved proteins, which predominantly present in extracellular matrix and critical components numerous processes matrix. Interestingly, fibromodulin (FMOD), one members SLRP exists both as proteoglycan glycoprotein juveniles old‐aged individuals, respectively. Despite their physiological significance interesting variations carbohydrate composition, structural dynamics (e.g., evolution structure over time), 3D conformational preferences remains unexplored to date. In this study, molecular modeling techniques were used investigate effects changes composition on dynamics. A total 6µs all‐atom simulations performed three types systems: non‐glycosylated FMOD, form lacking keratan sulfate disaccharides with GAGs. Substantial found FMOD between states. These accompanied modifications curved‐solenoid architecture well local solvent accessibilities some residues. relatively rigid, motif, sequence across various species, was identified unstructured N‐terminal domain. This motif highly accessible states, despite its proximity chains. two features (rigididy high accessibility) suggest key role for protein‐protein interactions established Fibromodulin. Overall, study provides insight into how influences protein functions.

Language: Английский

Citations

0