Protein folding does not prevent the nonclassical export of FGF1 and S100A13.
Newly synthesized proteins are usually exported through the endoplasmic reticulum (ER) and Golgi due to the presence in their primary sequence of a hydrophobic signal peptide that is recognized by the ER translocation system. However, some secreted proteins lack a signal peptide and are exported independently of ER-Golgi. Fibroblast growth factor (FGF)1 is included in this group of polypeptides, as well as S100A13 that is a small calcium-binding protein critical for FGF1 export. Classically secreted proteins are transported into ER in their unfolded states. To determine the role of protein tertiary structure in FGF1 export through the cell membrane, we produced the chimeras of FGF1 and S100A13 with dihydrofolate reductase (DHFR). The specific DHFR inhibitor, aminopterin, prevents its unfolding. We found that aminopterin did not inhibit the release of FGF1:DHFR and S100A13:DHFR. Thus, FGF1 and S100A13 can be exported in folded conformation.
Graziani
Irene
I
Maine Medical Center Research Institute, Scarborough, 81 Research Dr., Scarborough, ME 04074, USA.
Doyle
Andrew
A
Sterling
Sarah
S
Kirov
Alek
A
Tarantini
Francesca
F
Landriscina
Matteo
M
Kumar
Thallapuranam Krishnaswamy S
TK
Neivandt
David
D
Prudovsky
Igor
I
D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D017510:Protein Folding; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D009418:S100 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D021382:Protein Sorting Signals; D009418:S100 Proteins; D016220:Fibroblast Growth Factor 1