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 | 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> | ||