| RRC ID |
85875
|
| 著者 |
Kosuge H, Nakakido M, de Vega S, Ohnuma SI, Tsumoto K.
|
| タイトル |
PRELP functions via multiple interactions with intrinsically weak affinity relying on ECM anchoring and remodeling.
|
| ジャーナル |
Sci Rep
|
| Abstract |
A small leucine-rich repeat proteoglycan PRELP is responsible for various biological functions. Here, to quantitatively assess the ligand binding of PRELP and its relevance to physiological activities, we validated the premise that PRELP multi-specifically binds to TGFβ1, IGFI-R, and p75NTR with relatively weak, micromolar range of affinities using surface plasmon resonance analysis. Results of a direct binding assay using N-terminal-truncated PRELP and chimeric PRELP and a dual injection assay to evaluate the binding regions and competitiveness suggested that PRELP interacts with the ligands via different but partially overlapping regions in the leucine-rich repeat domain. RNA-seq analysis revealed that PRELP greatly promotes gene expression of various extracellular matrix (ECM) components in A549 lung carcinoma cells, also at micromolar concentration. Since we reasoned that ECM anchoring contributes to an increase of apparent local concentrations of PRELP required for the weak affinity interactions, we validated the direct binding and co-localization of PRELP with ECM proteins using ELISA analysis and immunofluorescence staining. Results of this study suggest that PRELP modulates multiple interactions with intrinsically weak binding affinities through the anchoring to ECM proteins and also promotes the ECM protein expression to maintain the preferred environment to exert the molecular functions.
|
| 巻・号 |
15(1)
|
| ページ |
24634
|
| 公開日 |
2025-7-9
|
| DOI |
10.1038/s41598-025-09018-7
|
| PII |
10.1038/s41598-025-09018-7
|
| PMID |
40634432
|
| PMC |
PMC12241546
|
| MeSH |
A549 Cells
Extracellular Matrix* / metabolism
Extracellular Matrix Proteins / metabolism
Humans
Protein Binding
Proteoglycans* / chemistry
Proteoglycans* / genetics
Proteoglycans* / metabolism
Surface Plasmon Resonance
Transforming Growth Factor beta1 / metabolism
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
A549 |
