S100A13-lipid interactions-role in the non-classical release of the acidic fibroblast growth factor.
S100A13 is a 98-amino acid, calcium binding protein. It is known to participate in the non-classical secretion of signal peptide-less proteins, such as the acidic fibroblast growth factor. In this study, we investigate the lipid binding properties of S10013 using a number of biophysical techniques, including multidimensional NMR spectroscopy. Isothermal titration calorimetry and steady state fluorescence experiments show that apoS100A13 exhibits preferential binding to small unilamelar vesicles of l-phosphatidyl serine (pS). In comparison, Ca2+-bound S100A13 is observed to bind weakly to unilamelar vesicles (SUVs) of pS. Equilibrium thermal unfolding and limited trypsin digestion analysis reveal that apoS100A13 is significantly destabilized upon binding to SUVs of pS. Results of the far UV circular dichroism and ANS (8-anilino-1-napthalene sufonate) binding experiments indicate a subtle conformational change resulting in the increase in the solvent-accessible hydrophobic surface in the protein. Availability of the solvent-exposed hydrophobic surface(s) in apoS10013 facilitates its interaction with the lipid vesicles. Our data suggest that Ca2+ binding dictates the membrane binding affinity of S100A13. Based on the results of this study, a model describing the sequence of molecular events that possibly can occur during the non-classical secretion of FGF-1 is presented.
Kathir
Karuppanan Muthusamy
KM
Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA.
Ibrahim
Khalil
K
Rajalingam
Dakshinamurthy
D
Prudovsky
Igor
I
Yu
Chin
C
Kumar
Thallapuranam Krishnaswamy Suresh
TK
D001665:Binding Sites; D002942:Circular Dichroism; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry* / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D009418:S100 Proteins / Q000737:chemistry* / Q000378:metabolism
D008055:Lipids; D009418:S100 Proteins; D016220:Fibroblast Growth Factor 1