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


Abstract

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 PDB Entries

Structure ID Release Date Resolution Structure Title
1OOH 2003-09-02 1.25 Complex of Drosophila odorant binding protein LUSH with butanol
2GTE 2007-06-12 1.4 Drosophila OBP LUSH bound to attractant pheromone 11-cis-vaccenyl acetate
1OOG 2003-09-02 1.45 Complex of Drosophila odorant binding protein LUSH with propanol
1OOF 2003-09-02 1.49 Complex of Drosophila odorant binding protein LUSH with ethanol
1T14 2005-04-26 1.86 Crystal structure of LUSH from Drosophila melanogaster: apo protein
3B7A 2008-02-05 1.9 Complex of S52A Substituted Droposphila LUSH protein with Ethanol
3B6X 2008-02-05 2.0 Complex of S52A Substituted Drosophila LUSH protein with Butanol
3B87 2008-02-05 2.0 Complex of T57A Substituted Droposphila LUSH protein with Butanol
3B88 2008-02-05 2.0 Complex of T57A Substituted Drosophila LUSH Protein with Ethanol
2QDI 2008-06-03 2.0 Drosophila OBP LUSH D118A mutation
3B86 2008-02-05 2.0 Crystal structure of T57S substituted LUSH protein complexed with ethanol
1OOI 2003-09-02 2.04 Crystal structure of LUSH from Drosophila melanogaster at pH 6.5

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 General odorant-binding protein lush O02372 OB76A_DROME