Odorant binding protein: Difference between revisions
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The protein natural ligand is the moth pheromone <scene name='68/683383/Bombykol_ligand_in_2p71/1'>Bombykol</scene>. However, it was demonstrated that other molecules can also bound to the protein cavity <ref>doi: 10.1016/j.str.2007.07.013</ref>. The interaction with the ligand is being made by 4 alpha helices 1, 4, 5 and 6 in the core of the protein, which form the binding cavity <ref>doi: 10.1016/S1074-5521(00)00078-8</ref>. | The protein natural ligand is the moth pheromone <scene name='68/683383/Bombykol_ligand_in_2p71/1'>Bombykol</scene>. However, it was demonstrated that other molecules can also bound to the protein cavity <ref>doi: 10.1016/j.str.2007.07.013</ref>. The interaction with the ligand is being made by 4 alpha helices 1, 4, 5 and 6 in the core of the protein, which form the binding cavity <ref>doi: 10.1016/S1074-5521(00)00078-8</ref>. | ||
Inside the binding cavity, <scene name='68/683383/Residues_interacting/1'>non-charged residues</scene> are interacting with the pheromone, mainly by van der waals bounds. Out of those residues, some are conserved across OBP of lepidopteran (<font color=#8DB600><b>in green</b></font>), and the rest are conserved in lepidopteran PBP only (<font color=#318CE7><b>in light blue</b></font>). | Inside the binding cavity, <scene name='68/683383/Residues_interacting/1'>non-charged residues</scene> are interacting with the pheromone, mainly by van der waals bounds. Out of those residues, some are conserved across OBP of lepidopteran (<font color=#8DB600><b>in green</b></font>), and the rest are conserved in lepidopteran PBP only (<font color=#318CE7><b>in light blue</b></font>). | ||
In addition, the hydroxyl group of the pheromone bombykol forms a <scene name='68/683383/Ser56_interaction_with_oxg/2'>hydrogen bond with the | In addition, the hydroxyl group of the pheromone bombykol forms a <scene name='68/683383/Ser56_interaction_with_oxg/2'>hydrogen bond with the side chain of Ser56</scene>, Ser56 in red, oxygens are in purple (O–O distance of 2.8 Å). | ||
====Protein conformations==== | ====Protein conformations==== | ||
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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 | 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">DOI: 10.1007/s00359-009-0461-4</ref> 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">DOI: 10.1007/s00359-009-0461-4</ref> 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==== | ||
