Partially structured self-associating states of acidic fibroblast growth factor.


Abstract

A combination of near- and far-UV circular dichroism, Fourier-transform infrared spectroscopy, tryptophan fluorescence, size-exclusion chromatography, and a fluorescent extrinsic hydrophobic probe has been employed to characterize partially structured states of human recombinant acidic fibroblast growth factor (aFGF). At low pH, the addition of specific polyanionic ligands or moderate amounts of salts induces states with high secondary but low tertiary structure content. At neutral pH, intermediate amounts of chaotropic agents impose similar partially structured conformational states which also display noncooperative unfolding transitions. Kinetic evidence indicates that similar forms of the protein exist in the first few hundred milliseconds in the refolding pathway of aFGF. The kinetics of their formation appear to be temperature-independent, implying lack of an energy barrier, which is characteristic for further slow folding into the native state. Unlike the native and fully unfolded states, these partially structured conformations exhibit very low solubility, resulting in irreversible aggregation. Potential physiological implications of the existence of such "molten globule" states with regard to the growth factor's transport and biological activity are considered. Study holds ProTherm entries: 4561 Extra Details: additive : EDTA(0.1 mM), tertiary structure; conformational states; noncooperative;,solubility; molten globule

Submission Details

ID: Kshaji3P

Submitter: Connie Wang

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

Version: 1

Publication Details
Mach H;Ryan JA;Burke CJ;Volkin DB;Middaugh CR,Biochemistry (1993) Partially structured self-associating states of acidic fibroblast growth factor. PMID:7688566
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
2M49 2013-12-18 Structural Insights into Human S100B and Basic Fibroblast Growth Factor (FGF2) Interaction
1BLD 1996-11-08 BASIC FIBROBLAST GROWTH FACTOR (FGF-2) MUTANT WITH CYS 78 REPLACED BY SER AND CYS 96 REPLACED BY SER, NMR
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
4OEG 2014-07-09 1.6 Crystal Structure Analysis of FGF2-Disaccharide (S9I2) complex
1BFG 1994-01-31 1.6 CRYSTAL STRUCTURE OF BASIC FIBROBLAST GROWTH FACTOR AT 1.6 ANGSTROMS RESOLUTION
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
1BAS 1993-10-31 1.9 THREE-DIMENSIONAL STRUCTURES OF ACIDIC AND BASIC FIBROBLAST GROWTH FACTORS
1BFB 1996-04-03 1.9 BASIC FIBROBLAST GROWTH FACTOR COMPLEXED WITH HEPARIN TETRAMER FRAGMENT
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
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)
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
1BFC 1996-04-03 2.2 BASIC FIBROBLAST GROWTH FACTOR COMPLEXED WITH HEPARIN HEXAMER FRAGMENT
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