Structurally homologous all beta-barrel proteins adopt different mechanisms of folding.


Acidic fibroblast growth factors from human (hFGF-1) and newt (nFGF-1) (Notopthalamus viridescens) are 16-kDa, all beta-sheet proteins with nearly identical three-dimensional structures. Guanidine hydrochloride (GdnHCl)-induced unfolding of hFGF-1 and nFGF-1 monitored by fluorescence and far-UV circular dichroism (CD) shows that the FGF-1 isoforms differ significantly in their thermodynamic stabilities. GdnHCl-induced unfolding of nFGF-1 follows a two-state (Native state to Denatured state(s)) mechanism without detectable intermediate(s). By contrast, unfolding of hFGF-1 monitored by fluorescence, far-UV circular dichroism, size-exclusion chromatography, and NMR spectroscopy shows that the unfolding process is noncooperative and proceeds with the accumulation of stable intermediate(s) at 0.96 M GdnHCl. The intermediate (in hFGF-1) populated maximally at 0.96 M GdnHCl has molten globule-like properties and shows strong binding affinity to the hydrophobic dye, 1-Anilino-8-naphthalene sulfonate (ANS). Refolding kinetics of hFGF-1 and nFGF-1 monitored by stopped-flow fluorescence reveal that hFGF-1 and nFGF-1 adopts different folding mechanisms. The observed differences in the folding/unfolding mechanisms of nFGF-1 and hFGF-1 are proposed to be either due to differential stabilizing effects of the charged denaturant (Gdn(+) Cl(-)) on the intermediate state(s) and/or due to differences in the structural interactions stabilizing the native conformation(s) of the FGF-1 isoforms. Study holds ProTherm entries: 16671, 16672, 16673, 16674 Extra Details: two-state; stable intermediate; molten globule; structural interactions

Submission Details


Submitter: Connie Wang

Submission Date: April 24, 2018, 8:48 p.m.

Version: 1

Publication Details
Srimathi T;Kumar TK;Kathir KM;Chi YH;Srisailam S;Lin WY;Chiu IM;Yu C,Biophys. J. (2003) Structurally homologous all beta-barrel proteins adopt different mechanisms of folding. PMID:12829501
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 UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Fibroblast growth factor 1 Q7SIF8 FGF1_NOTVI
94.6 Fibroblast growth factor 1 Q6I6M7 FGF1_CYNPY
100.0 Fibroblast growth factor 1 P05230 FGF1_HUMAN
100.0 Fibroblast growth factor 1 Q5NVQ3 FGF1_PONAB
97.9 Fibroblast growth factor 1 P34004 FGF1_MESAU
98.0 Fibroblast growth factor 1 P20002 FGF1_PIG
96.4 Fibroblast growth factor 1 P61148 FGF1_MOUSE
96.4 Fibroblast growth factor 1 P61149 FGF1_RAT
92.3 Fibroblast growth factor 1 P03968 FGF1_BOVIN
90.7 Fibroblast growth factor 1 Q7M303 FGF1_SHEEP
90.3 Fibroblast growth factor 1 P19596 FGF1_CHICK
91.5 Fibroblast growth factor 1 Q9N1S8 FGF1_CAPCA