Odorant binding protein: Difference between revisions

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'''Conformation transition mechanism:'''
'''Conformation transition mechanism:'''
The c-terminus of the protein bears mostly <scene name='68/683383/Hydrophobic_resid/1'>non-polar amino acids</scene>. Yet on the surface of the helix there are three exceptional amino acids: Asp-132, Glu-137, and Glu-141, which are conserved in moth PBP <ref>doi: 10.1016/j.bbrc.2005.07.176</ref>. Of these, residues <scene name='68/683383/Asp132/1'>Asp-132</scene> (and Glu-141, if present) triggers the formation of the alpha-helix upon protonation at low pH. This causes the transition from the <scene name='68/683383/B_form_with_ligand/1'>"A form"</scene>, to the <scene name='68/683383/A_form_with_ligand/1'>"B form"</scene> and the ejaculation of the ligand from the binding pocket, which is replaced by the formatted alpha helix<ref>doi: 10.1016/j.bbrc</ref>.  
The c-terminus of the protein bears mostly <scene name='68/683383/Hydrophobic_resid/1'>non-polar amino acids</scene>. Yet on the surface of the helix there are three exceptional amino acids: Asp-132, Glu-137, and Glu-141, which are conserved in moth PBP <ref>doi: 10.1016/j.bbrc.2005.07.176</ref>. Of these, residues <scene name='68/683383/Asp132/1'>Asp-132</scene> (and Glu-141, if present) triggers the formation of the alpha-helix upon protonation at low pH. This causes the transition from the <scene name='68/683383/B_form_with_ligand/1'>"A form"</scene>, to the <scene name='68/683383/A_form_with_ligand/1'>"B form"</scene> and the ejaculation of the ligand from the binding pocket, which is replaced by the formatted alpha helix<ref>doi: 10.1016/j.bbrc</ref>.  
 
Studies on other Lepidopterans that show a similar pH dependent conformation suggests that this model is a general model moth PBP<ref name="Leal" />. Nonetheless, the enormous diversity among insects is not allowing us to assume this model is true for all insects' OBPs.
Studies on other Lepidopterans that show a similar pH dependent conformation suggests that this model is a general model moth PBP<ref name="Leal" />.  
Nonetheless, the enormous diversity among insects is not allowing us to assume this model is true for all insects' OBPs.
[[Image:N model extended.png|thumb|upright=2.5|Figure 1. The events prior the neuron excitation, following the "N model" suggested by Kaissling (2009)<ref name="Kaissling 2009" />: The pheromone enters the sensillar lymph through a pore in cuticle. The pheromone can then be degraded by the ODE (1) -or- bind to the A and B protein forms (2a and 2b, respectively).  When the complex arrives at the low pH near the membrane, the transition is in favor of the A-form, (3) in which the -c-terminus is forming an alpha helix inside the binding cavity, pushing out the pheromone. The activation of the complex of odorant receptor and coreceptor (OR:OR-CO), is induced by ether the complex of pheromone-PBP, or by the pheromone alone (5, two options). The B-form can also act as a scavenger, as it mediates the deactivation of the pheromone (6) and releases it to the ODE (6)]]  
[[Image:N model extended.png|thumb|upright=2.5|Figure 1. The events prior the neuron excitation, following the "N model" suggested by Kaissling (2009)<ref name="Kaissling 2009" />: The pheromone enters the sensillar lymph through a pore in cuticle. The pheromone can then be degraded by the ODE (1) -or- bind to the A and B protein forms (2a and 2b, respectively).  When the complex arrives at the low pH near the membrane, the transition is in favor of the A-form, (3) in which the -c-terminus is forming an alpha helix inside the binding cavity, pushing out the pheromone. The activation of the complex of odorant receptor and coreceptor (OR:OR-CO), is induced by ether the complex of pheromone-PBP, or by the pheromone alone (5, two options). The B-form can also act as a scavenger, as it mediates the deactivation of the pheromone (6) and releases it to the ODE (6)]]  
====Receptor activation====
====Receptor activation====
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*'''Activation by the pheromone alone'''  
*'''Activation by the pheromone alone'''  
This model is supported by the pH dependent conformation transition, that is described above. The bulk of the sensillar lymph is in neutral pH (6.5-7), while environment near the dendrite membrane bears a low pH (4.5), due to the negative charges on the surface of the membrane <ref>DOI: 10.1016/0040-8166(84)90004-1</ref>, which cause the accumulation of positively charged kations near the membrane surface (20-50 nm)<ref name="Kaissling 2009" />. According to this model (illustrated in [[figure 1]]), the pheromone is entering the sensillar lymph through a pore in the cuticle, then it can be either degraded by odorant degrading enzymes (ODE) or bind to a PBP (of both forms). Once the complex is arriving to the low pH environment near the dendrite membrane the PBP will shift to the A-form, thereby ejaculating the ligand from the binding pocket, allowing it to activate the OR:CO-OR complex and the cellular signal transduction begins.       
This model is supported by the pH dependent conformation transition, that is described above. The bulk of the sensillar lymph is in neutral pH (6.5-7), while environment near the dendrite membrane bears a low pH (4.5), due to the negative charges on the surface of the membrane <ref>DOI: 10.1016/0040-8166(84)90004-1</ref>, which cause the accumulation of positively charged kations near the membrane surface (20-50 nm)<ref name="Kaissling 2009" />. According to this model, the pheromone is entering the sensillar lymph through a pore in the cuticle, then it can be either degraded by odorant degrading enzymes (ODE) or bind to a PBP (of both forms). Once the complex is arriving to the low pH environment near the dendrite membrane the PBP will shift to the A-form, thereby ejaculating the ligand from the binding pocket, allowing it to activate the OR:CO-OR complex and the cellular signal transduction begins.       
   
   


*'''Activation by the complex pheromone-PBP'''
*'''Activation by the complex pheromone-PBP'''
An alternative mode of action was proposed for the receptor activation in Drosophila, where it was found that the complex of pheromone-PBP is required for the activity of pheromone-sensitive neurons <ref>DOI: 10.1016/j.neuron.2004.12.031<ref/><ref>doi: 10.1016/j.cell.2008.04.046<ref/>  
An alternative mode of action was proposed for the receptor activation in ''Drosophila melanogaster'', where it was found that the complex of pheromone-PBP is required for the activity of pheromone-sensitive neurons <ref>DOI: 10.1016/j.neuron.2004.12.031<ref/><ref>doi: 10.1016/j.cell.2008.04.046<ref/>  


</StructureSection>
</StructureSection>