2QDI

Drosophila OBP LUSH D118A mutation

Summary for 2QDI

• Entry DOI: 10.2210/pdb2qdi/pdb
• Related: 1OOF 1OOG 1OOH 1OOI 1T14 2GTE
• Descriptor: General odorant-binding protein lush, TRIETHYLENE GLYCOL (3 entities in total)
• Functional Keywords: odorant binding protein, obp, pheromone binding protein, pbp, transport protein
• Biological source: Drosophila melanogaster (Fruit fly)
• Cellular location: Secreted: O02372
• Total number of polymer chains: 2
• Total formula weight: 28643.34

Authors

Laughlin, J.D.,Jones, D.N.M. (deposition date: 2007-06-20, release date: 2008-06-03, Last modification date: 2024-11-20)

Primary citation

Laughlin, J.D.,Ha, T.S.,Jones, D.N.,Smith, D.P.
Activation of pheromone-sensitive neurons is mediated by conformational activation of pheromone-binding protein.
Cell(Cambridge,Mass.), 133:1255-1265, 2008

PubMed Abstract: Detection of volatile odorants by olfactory neurons is thought to result from direct activation of seven-transmembrane odorant receptors by odor molecules. Here, we show that detection of the Drosophila pheromone, 11-cis vaccenyl acetate (cVA), is instead mediated by pheromone-induced conformational shifts in the extracellular pheromone-binding protein, LUSH. We show that LUSH undergoes a pheromone-specific conformational change that triggers the firing of pheromone-sensitive neurons. Amino acid substitutions in LUSH that are predicted to reduce or enhance the conformational shift alter sensitivity to cVA as predicted in vivo. One substitution, LUSH(D118A), produces a dominant-active LUSH protein that stimulates T1 neurons through the neuronal receptor components Or67d and SNMP in the complete absence of pheromone. Structural analysis of LUSH(D118A) reveals that it closely resembles cVA-bound LUSH. Therefore, the pheromone-binding protein is an inactive, extracellular ligand converted by pheromone molecules into an activator of pheromone-sensitive neurons and reveals a distinct paradigm for detection of odorants.

PubMed: 18585358
DOI: 10.1016/j.cell.2008.04.046

Experimental method

X-RAY DIFFRACTION (2 Å)