Structural highlights
Function
[OB76A_DROME] Odorant-binding protein required for olfactory behavior and for activity of pheromone-sensitive neurons. Binds to alcohols and mediates avoidance behavior to high concentrations of alcohols, the alcohol-binding possibly resulting in activation of receptors on T2B neurons, the activation of these receptors inhibiting these neurons. Acts in concert with Snmp and lush to capture cVA molecules on the surface of Or67d expressing olfactory dendrites and facilitate their transfer to the odorant-receptor Orco complex. Required for cVA response, probably by binding to VA. May act by serving as an adapter that bridges the presence of gaseous pheromone molecules, cVA, to activation of specific neuronal receptors expressed on T1 olfactory neurons, possibly via a specific conformational change induced by cVA that in turn activates T1 receptors. T1 neurons are excited by the pheromone VA, while T2 neurons are inhibited by alcohols. Also binds to phthalates.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Activation of pheromone-sensitive neurons is mediated by conformational activation of pheromone-binding protein.,Laughlin JD, Ha TS, Jones DN, Smith DP Cell. 2008 Jun 27;133(7):1255-65. PMID:18585358[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kim MS, Repp A, Smith DP. LUSH odorant-binding protein mediates chemosensory responses to alcohols in Drosophila melanogaster. Genetics. 1998 Oct;150(2):711-21. PMID:9755202
- ↑ Kim MS, Smith DP. The invertebrate odorant-binding protein LUSH is required for normal olfactory behavior in Drosophila. Chem Senses. 2001 Feb;26(2):195-9. PMID:11238251
- ↑ Zhou JJ, Zhang GA, Huang W, Birkett MA, Field LM, Pickett JA, Pelosi P. Revisiting the odorant-binding protein LUSH of Drosophila melanogaster: evidence for odour recognition and discrimination. FEBS Lett. 2004 Jan 30;558(1-3):23-6. PMID:14759510 doi:10.1016/S0014-5793(03)01521-7
- ↑ Xu P, Atkinson R, Jones DN, Smith DP. Drosophila OBP LUSH is required for activity of pheromone-sensitive neurons. Neuron. 2005 Jan 20;45(2):193-200. PMID:15664171 doi:10.1016/j.neuron.2004.12.031
- ↑ Ha TS, Smith DP. A pheromone receptor mediates 11-cis-vaccenyl acetate-induced responses in Drosophila. J Neurosci. 2006 Aug 23;26(34):8727-33. PMID:16928861 doi:10.1523/JNEUROSCI.0876-06.2006
- ↑ Benton R, Vannice KS, Vosshall LB. An essential role for a CD36-related receptor in pheromone detection in Drosophila. Nature. 2007 Nov 8;450(7167):289-93. Epub 2007 Oct 17. PMID:17943085 doi:10.1038/nature06328
- ↑ Laughlin JD, Ha TS, Jones DN, Smith DP. Activation of pheromone-sensitive neurons is mediated by conformational activation of pheromone-binding protein. Cell. 2008 Jun 27;133(7):1255-65. PMID:18585358 doi:10.1016/j.cell.2008.04.046
