Effect of n-alcohols on the structure and stability of the Drosophila odorant binding protein LUSH.


LUSH is an odorant binding protein expressed in the olfactory organs of Drosophila melanogaster that is required for the detection of alcohol in adult flies. Here we demonstrate that, in the absence of ligand, in vitro LUSH exists in a partial molten globule state. The presence of short-chain n-alcohols at pharmacologically relevant concentrations less than 50 mM shifts the conformational equilibrium to a more compact state that exhibits reduced binding of the fluorescent dye 1-anilino-8-naphthalenesulfonic acid. Equilibrium unfolding studies of LUSH-alcohol complexes reveal that, for a series of short-chain n-alcohols, each methylene group can contribute approximately 1 K cal mol(-1) to the overall stability of the protein-alcohol complex. Using NMR spectroscopy, we have identified the regions of LUSH that show increased conformational stability on binding alcohols. These residues primarily line the alcohol-binding pocket. The results presented here provide a direct measure of the degree of stability that alcohol imparts on LUSH. These observations may represent a model for how ethanol can stabilize alternative protein conformations in alcohol-sensitive human proteins and ultimately lead to the observed changes in higher order function throughout the central nervous system. Study holds ProTherm entries: 19830, 19831, 19832, 19833 Extra Details: olfactory organs; binding; alcohols; alcohol-sensitive human proteins

Submission Details

ID: 9voukVFu3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:52 p.m.

Version: 1

Publication Details
Bucci BK;Kruse SW;Thode AB;Alvarado SM;Jones DN,Biochemistry (2006) Effect of n-alcohols on the structure and stability of the Drosophila odorant binding protein LUSH. PMID:16460016
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 General odorant-binding protein lush O02372 OB76A_DROME