Mechanisms of Olfaction in Insects - ResearchSpace@Auckland ...
Mechanisms of Olfaction in Insects - ResearchSpace@Auckland ...
Mechanisms of Olfaction in Insects - ResearchSpace@Auckland ...
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General Introduction 10<br />
opposed to wild type flies that avoid high alcohol levels. Further research with LUSH<br />
mutants showed that this OBP is <strong>in</strong>volved <strong>in</strong> activity <strong>of</strong> the pheromone-sensitive<br />
neurons. The activity <strong>of</strong> the male-specific lipid, 11-cis vaccenyl acetate (cVA) that<br />
causes aggregation <strong>in</strong> wild type flies is lost <strong>in</strong> mutants. The activity <strong>of</strong> this pheromone<br />
is restored with transgenic expression <strong>of</strong> the LUSH prote<strong>in</strong> suggest<strong>in</strong>g that the loss <strong>of</strong><br />
function <strong>in</strong> mutants is specifically due to absence <strong>of</strong> LUSH <strong>in</strong> the pheromone<br />
sensitive sensilla (Zhou et al., 2004; Xu et al., 2005). Further to this, Laughl<strong>in</strong> et al.<br />
(2008) showed through solv<strong>in</strong>g the structures <strong>of</strong> various bound and unbound states <strong>of</strong><br />
LUSH, as well as <strong>of</strong> several LUSH prote<strong>in</strong>s with po<strong>in</strong>t mutations that the cVA bound<br />
LUSH acts as an activator <strong>of</strong> pheromone sensitive neurons (Laughl<strong>in</strong> et al., 2008).<br />
When cVA is bound to LUSH, a conformational change occurs that disrupts a salt<br />
bridge <strong>in</strong> LUSH and causes shifts <strong>in</strong> its surface loop. This altered state <strong>of</strong> LUSH then<br />
activates the pheromone neuron, as depicted <strong>in</strong> Figure 1.2. The salt bridge is<br />
ma<strong>in</strong>ta<strong>in</strong>ed <strong>in</strong> the unbound state and when an alcohol such as butanol is bound to<br />
LUSH. This <strong>in</strong>dicates that the OBP/ligand complex <strong>in</strong>teracts with the PR (Laughl<strong>in</strong> et<br />
al., 2008).<br />
Figure 1.2: Odorant receptor activation as depicted by Laughl<strong>in</strong> et al. (2008). The<br />
formation <strong>of</strong> the cVA/LUSH complex results <strong>in</strong> a conformational change <strong>of</strong> LUSH<br />
mak<strong>in</strong>g it an active ligand that <strong>in</strong>teracts directly with the pheromone receptor. From<br />
Stowers and Logan (2008).<br />
PR