Effect of polyanions on the unfolding of acidic fibroblast growth factor.


Abstract

The urea-induced unfolding of acidic fibroblast growth factor (aFGF) in the presence and absence of various polyanions has been quantitatively examined by fluorescence spectroscopy. In the absence of a stabilizing polyanion, the apparent free energy of unfolding of aFGF is 6.5 kcal mol-1. The presence of equimolar or greater amounts of heparin stabilizes aFGF from unfolding by more than 2.5 kcal mol-1 and slows the rate of unfolding by greater than 2000-fold. The ability of heparin to stabilize aFGF is critically dependent upon many factors including the number of aFGF molecules bound to the heparin chain, ionic strength, temperature, and the extent of sulfation of the polysaccharide. The presence of similar amounts of other polyanions such as sulfated beta-cyclodextrin or heparan sulfate also stabilizes aFGF to a similar extent as heparin. Additional experiments demonstrate that increasing charge density enhances the ability of polyanions such as sulfated beta-cyclodextrins, phosphorylated inositols, and modified heparins to protect aFGF from urea-induced unfolding. Study holds ProTherm entries: 4576, 4577, 4578, 4579, 4580 Extra Details: polyanions; sulfation; sulfated beta-cyclodextrin; heparin

Submission Details

ID: pPduruz34

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:26 p.m.

Version: 1

Publication Details
Burke CJ;Volkin DB;Mach H;Middaugh CR,Biochemistry (1993) Effect of polyanions on the unfolding of acidic fibroblast growth factor. PMID:7686045
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1BLD 1996-11-08 BASIC FIBROBLAST GROWTH FACTOR (FGF-2) MUTANT WITH CYS 78 REPLACED BY SER AND CYS 96 REPLACED BY SER, NMR
2M49 2013-12-18 Structural Insights into Human S100B and Basic Fibroblast Growth Factor (FGF2) Interaction
1BLA 1996-11-08 BASIC FIBROBLAST GROWTH FACTOR (FGF-2) MUTANT WITH CYS 78 REPLACED BY SER AND CYS 96 REPLACED BY SER, NMR
4OEE 2014-07-09 1.5 Crystal Structure Analysis of FGF2-Disaccharide (S3I2) complex
4FGF 1993-07-15 1.6 REFINEMENT OF THE STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION AND ANALYSIS OF PRESUMED HEPARIN BINDING SITES BY SELENATE SUBSTITUTION
1BFG 1994-01-31 1.6 CRYSTAL STRUCTURE OF BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION
4OEG 2014-07-09 1.6 Crystal Structure Analysis of FGF2-Disaccharide (S9I2) complex
2FGF 1992-01-15 1.77 THREE-DIMENSIONAL STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR, A STRUCTURAL HOMOLOG OF INTERLEUKIN 1BETA
4OEF 2014-07-09 1.8 Crystal Structure Analysis of FGF2-Disaccharide (S6I2) complex
5X1O 2018-03-07 1.9 PI(4,5)P2 lipid binding induced a reorientation of FGF2 molecules near membrane surface to facilitate the unconventional oligomerization-dependent secretion process as revealed by a combined FTIR/NMR/X-ray study
1BFB 1996-04-03 1.9 BASIC FIBROBLAST GROWTH FACTOR COMPLEXED WITH HEPARIN TETRAMER FRAGMENT
1BAS 1993-10-31 1.9 THREE-DIMENSIONAL STRUCTURES OF ACIDIC AND BASIC FIBROBLAST GROWTH FACTORS
1BFF 1997-06-16 2.0 THE 154 AMINO ACID FORM OF HUMAN BASIC FIBROBLAST GROWTH FACTOR
1EV2 2000-05-31 2.2 CRYSTAL STRUCTURE OF FGF2 IN COMPLEX WITH THE EXTRACELLULAR LIGAND BINDING DOMAIN OF FGF RECEPTOR 2 (FGFR2)
1BFC 1996-04-03 2.2 BASIC FIBROBLAST GROWTH FACTOR COMPLEXED WITH HEPARIN HEXAMER FRAGMENT
1FGA 1993-07-15 2.2 REFINEMENT OF THE STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION AND ANALYSIS OF PRESUMED HEPARIN BINDING SITES BY SELENATE SUBSTITUTION
1IIL 2001-05-09 2.3 CRYSTAL STRUCTURE OF PRO253ARG APERT MUTANT FGF RECEPTOR 2 (FGFR2) IN COMPLEX WITH FGF2
2BFH 1994-01-31 2.5 CRYSTAL STRUCTURE OF BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION
1II4 2001-05-09 2.7 CRYSTAL STRUCTURE OF SER252TRP APERT MUTANT FGF RECEPTOR 2 (FGFR2) IN COMPLEX WITH FGF2
1CVS 2000-01-28 2.8 CRYSTAL STRUCTURE OF A DIMERIC FGF2-FGFR1 COMPLEX
1FQ9 2000-09-27 3.0 CRYSTAL STRUCTURE OF A TERNARY FGF2-FGFR1-HEPARIN COMPLEX

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
99.3 Fibroblast growth factor 2 P48799 FGF2_RABIT
92.2 Fibroblast growth factor 2 P48800 FGF2_CHICK
92.9 Fibroblast growth factor 2 P48798 FGF2_MONDO
96.6 Fibroblast growth factor 2 P15655 FGF2_MOUSE
97.3 Fibroblast growth factor 2 P13109 FGF2_RAT
98.1 Fibroblast growth factor 2 P20003 FGF2_SHEEP
98.7 Fibroblast growth factor 2 P03969 FGF2_BOVIN
100.0 Fibroblast growth factor 2 Q5IS69 FGF2_PANTR
100.0 Fibroblast growth factor 2 P09038 FGF2_HUMAN
91.1 Fibroblast growth factor 2 Q60487 FGF2_CAVPO