Beta-sheet proteins with nearly identical structures have different folding intermediates.


The folding mechanisms of two proteins in the family of intracellular lipid binding proteins, ileal lipid binding protein (ILBP) and intestinal fatty acid binding protein (IFABP), were examined. The structures of these all-beta-proteins are very similar, with 123 of the 127 amino acids of ILBP having backbone and C(beta) conformations nearly identical to those of 123 of the 131 residues of IFABP. Despite this structural similarity, the sequences of these proteins have diverged, with 23% sequence identity and an additional 16% sequence similarity. The folding process was completely reversible, and no significant concentrations of intermediates were observed by circular dichroism or fluorescence at equilibrium for either protein. ILBP was less stable than IFABP with a midpoint of 2. 9 M urea compared to 4.0 M urea for IFABP. Stopped-flow kinetic studies showed that both the folding and unfolding of these proteins were not monophasic, suggesting that either multiple paths or intermediate states were present during these processes. Proline isomerization is unlikely to be the cause of the multiphasic kinetics. ILBP had an intermediate state with molten globule-like spectral properties, whereas IFABP had an intermediate state with little if any secondary structure during folding and unfolding. Double-jump experiments showed that these intermediates appear to be on the folding path for each protein. The folding mechanisms of these proteins were markedly different, suggesting that the different sequences of these two proteins dictate different paths through the folding landscape to the same final structure. Study holds ProTherm entries: 7851, 7852, 7853, 7854 Extra Details: additive : EDTA(0.1 mM), lipid binding proteins; intermediate states; proline,isomerization; folding mechanisms

Submission Details

ID: zkni2RZA4

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:35 p.m.

Version: 1

Publication Details
Dalessio PM;Ropson IJ,Biochemistry (2000) Beta-sheet proteins with nearly identical structures have different folding intermediates. PMID:10653629
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 Fatty acid-binding protein, liver P02692 FABPL_RAT
93.7 Fatty acid-binding protein, liver P12710 FABPL_MOUSE
100.0 Gastrotropin P80020 FABP6_RAT
94.5 Gastrotropin P51162 FABP6_MOUSE
100.0 Fatty acid-binding protein, brain P55051 FABP7_RAT
97.0 Fatty acid-binding protein, brain P51880 FABP7_MOUSE
100.0 Fatty acid-binding protein, intestinal P02693 FABPI_RAT
92.4 Fatty acid-binding protein, intestinal P55050 FABPI_MOUSE