Folding of Fibroblast Growth Factor 1 Is Critical for Its Nonclassical Release
- Maine Medical Center Research Inst. (MMCRI), Scarborough, MA (United States); Univ. of Maine, Orono, MA (United States). Graduate School of Biomedical Science and Engineering
- Maine Medical Center Research Inst. (MMCRI), Scarborough, MA (United States)
- Univ. of Arkansas, Fayetteville, AR (United States). Dept. of Chemistry and Biochemistry
- Univ. of New England, Portland, MA (United States). College of Pharmacy
- Univ. of Maine, Orono, MA (United States). Graduate School of Biomedical Science and Engineering
- Univ. of Maine, Orono, MA (United States). Graduate School of Biomedical Science and Engineering; Univ. of New England, Portland, MA (United States). College of Pharmacy
Fibroblast growth factor 1 (FGF1), a ubiquitously expressed pro-angiogenic protein that is involved in tissue repair, carcinogenesis, and maintenance of vasculature stability, is released from the cells via a stress-dependent nonclassical secretory pathway. FGF1 secretion is a result of transmembrane translocation of this protein. It correlates with the ability of FGF1 to permeabilize membranes composed of acidic phospholipids. Like several other nonclassically exported proteins, FGF1 exhibits β-barrel folding. In order to assess the role of folding of FGF1 in its secretion, we applied targeted mutagenesis in combination with a complex of biophysical methods and molecular dynamics studies, followed by artificial membrane permeabilization and stress-induced release experiments. It has been demonstrated that a mutation of proline 135 located in the C-terminus of FGF1 results in (i) partial unfolding of FGF1, (ii) a decrease in FGF1’s ability to permeabilize bilayers composed of phosphatidylserine, and (iii) drastic inhibition of stress-induced FGF1 export. Thus, folding of FGF1 is critical for its nonclassical secretion.
- Research Organization:
- Univ. of Arkansas, Fayetteville, AR (United States)
- Sponsoring Organization:
- USDOE Advanced Research Projects Agency - Energy (ARPA-E); National Institutes of Health (NIH); National Science Foundation (NSF)
- Grant/Contract Number:
- FG02-01ER15161; P30 GM103392; TG-MCB120007; ACI-1053575
- OSTI ID:
- 1466969
- Journal Information:
- Biochemistry, Vol. 55, Issue 7; ISSN 0006-2960
- Publisher:
- American Chemical Society (ACS)Copyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
miRNA‐210‐3p regulates trophoblast proliferation and invasiveness through fibroblast growth factor 1 in selective intrauterine growth restriction
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journal | April 2019 |
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