Odorant binding protein

2015-01-28T11:55:42Z

Nurit Eliash:

==Introduction==
Odorant-binding protein (OBP) are soluble proteins which involve in the processes of odorant detection in the olfactory sensilla <ref name="Pelosi 2014">doi: 10.3389/fphys.2014.00320</ref>

Though functionally same, vertebrates and insects OBP have different origin and structure.
OBPs are important for insect olfaction. For instance, OBP76a (LUSH) in the fly [http://en.wikipedia.org/wiki/Drosophila_melanogaster ''Drosophila melanogaster''] is required for the detection of the pheromone vaccenyl acetate <ref name="Xu 2005">doi: 10.1016/j.neuron.2004.12.031</ref> and has been proven to adopt a conformation that activates the odorant receptor <ref name="Laughlin 2008">doi: 10.1016/j.cell.2008.04.046</ref>.
[[Image:Bombyx mori.jpg|thumb|upright=1|''Bombyx mori'', the silk moth, picture by [https://www.flickr.com/photos/depredator007/2522038240/ Fernando Cuenca]]]
[[Image:Bombykol.png|thumb|upright=1|Bombykol, a sex pheromone of ''Bombyx mori'', from [http://pubchem.ncbi.nlm.nih.gov/compound/Bombykol#section=Top PubChem]]]

==OBP in insects==
==== OBP Function ====
Despite five decades of intensive research, the exact roles of OBP and the mechanism by which the odorant receptor (OR) is activated are still in dispute <ref name="Leal">DOI: 10.1146/annurev-ento-120811-153635</ref><ref>DOI: 10.1007/s00359-009-0461-4</ref>.

'''A few functions have been suggested for OBP:'''

1. Solubelizing the odorant molecule and its transportation in the sensillar lymph.

2. Protecting the odorant molecule from the odorant degrading enzymes, in the sensillar lymph.

3. Activating of the odorant receptor on the dendrite membrane, by the odorant-OBP complex.

4. Mediating the deactivation of the odorant molecule after the activation of the receptor.

5. An organic anion (the protein has 9 negative charges).

Of all, the first role of OBP as an odorant solubilizer and carrier is generally accepted.

In order to explain the structure and function of these fascinating proteins, this page will further focus on a particular OBP - the well investigated ''[http://en.wikipedia.org/wiki/Bombyx_mori Bombyx mori]'' PBP: [http://www.uniprot.org/uniprot/P34174 BmorPBP].

====''Bombyx mori'' BmorPBP (lets talk about sex..)====
<StructureSection load='1ls8' size='340' side='right' caption='''Bombyx mori'' PBP -BmorPBP scene=''>
Pheromone binding proteins (PBPs) are specialized members of the insect odorant-binding protein (OBP) super-family.
The main purpose in the dult moth's short life is reproduction. In fact, the male and female moth invest all of theire energy and resourses hoping to reach to the ultimate goal- mating. This long journey begins when the female moth releases a sex pheromone, usualy in specific hours in the night <ref>doi: 10.1007/BF01946910</ref>.
BmorPBP was first identified in the ''B. mori'' male antennae by Krieger et al. in 1996 <ref>doi: 10.1016/0965-1748(95)00096-8</ref>, as the PBP of the first sex pheromone discovered ((E,Z)-10,12-hexadecadienol, or [http://en.wikipedia.org/wiki/Bombykol Bombykol]). The male moth needs to detect minute amount of the pheromone in the air, while following turbulent wind-born pheromone trail and response fast (experimental evidence shows a response time of 0.5 seconds<ref>doi: 10.1038/293161a0</ref>).

====BmorPBP structure and function====
The protein has 164 amino acids that forms 6-7 alpha helices (depends on the protein conformation). Three disulfide bonds formed by <scene name='68/683383/Cysteins6/1'>6 cystein </scene> residues tied four helices, and form the compact and robust structure of the protein. As expected from a soluble protein, its surface is covered with <scene name='68/683383/Charged_resid/1'>charged residues</scene>, which allows it to make interactions with the water molecule and solubilize in the sensillar lymph.

====BmorPBP - ligand binding====
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 (in green), and the rest are conserved in lepidopteran PBP only (in light blue).
In addition, the hydroxyl group of the pheromone bombykol forms a <scene name='68/683383/Ser56_interaction_with_oxg/2'>hydrogen bond with the sidechain of Ser56</scene>, Ser56 in red, oxygens are in purple (O–O distance of 2.8 Å).

====Protein conformations====
[[Image:A -B forms without ligand.png|thumb|upright=2|The A and B forms without ligand (PDB IDs: [[1gm0]] and [[1ls8]]).]]
BmorPBP has two conformations: The '''"closed form" (A)''' and the ''"open form" (B)''<ref>DOI: 10.1074/jbc.274.43.30950</ref>. The bombykol and the alpha-helix loacated in the c-terminus of the protein compete for the binding site: when the c-terminus is inside the binding cavity it get's an alpha helix shape, and the protien is in its "close form" (B), whereas in the "open form" (A) the c-terminus is outside of the protein and has no defined secondary structure. Binding experiments have shown that the B-form binds 15 times higher than the A-form <ref>doi: 10.1073/pnas.0501447102</ref>, therefore considered to be the carrier of the pheromone. The complex of the A-form and the pheromone, is then considered the form that activates the receptor.

The <scene name='68/683383/1dqe-1gm0/4'>transition between the two conformation</scene> is both pH and ligand dependent <ref>doi: 10.1073?pnas.251532998</ref><ref>DOI: 10.1016/j.bbrc.2005.07.176</ref><ref>doi: 10.1073/pnas.1317706110</ref>. In short, the B-form (c-terminus outside the cavity) occurs only at neutral pH and in the presence of the ligand. The A-form (c-terminus inside the cavity) occurs at both low and neutral pH, yet at the latter only in the absence of ligand. Therefore, in neutral pH when the ligand is binding to the protein in its A-form, the complex formation causes a change in conformation to the B-form. However, both A and B forms are equally distributed in the lymph.
{{Button Toggle AnimationOnPause}}

'''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>.

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)]]
====Receptor activation====
Two theories have been proposed for the activation of the odorant receptors located on the dendrtirte membrane. One theory suggests that the pheromone-PBP complex is needed for the receptor activation, while the second theory argue that the pheromone itself is sufficient for the activation of the receptor.

*'''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.

*'''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/>

</StructureSection>

== See also ==
*[[Odorant_binding_protein_3D_structures]]
*[[Chemical communication in arthropods]]
*[[Pheromone binding protein]]
== References ==
<references/>

File:2fjy A.pdb

2015-01-28T11:45:55Z

Nurit Eliash:

2015-01-27T12:48:55Z

Nurit Eliash:

[[Image:Sensilla.png|thumb|upright=1.5|Figure 1: Vertebrate (a), and insect (b) sensilla. Figure 1 from Kaupp (2010), used with permission of Prof. U. Benjamin Kaupp.]]
[[Image:Signal trunsdution - Sanchez 2009.jpg|thumb|right|upright=2|Figure 2.(a) Schematic representation of the general structure of an insect olfactory hair; (b) The first molecular steps of the insect chemosensory signaling transduction pathway. Figure 1 from Sánchez-Gracia et al.(2009)<ref>doi: 10.1038/hdy.2009.55</ref>, used with permission of Prof. Sa´nchez-Gracia.]]
[[Image:Vieira and Rozas 2011 fig7.JPG|thumb|upright=1.5|Figure 3. The evolution of the Chemosensory System. Blue boxes represent the aquatic lifestyle. Right: Presence or absence of the chemosensory gene families in extant species. Branch lengths are not to scale. Figure 7 from Vieira and Rozas (2011), used with permission of Prof Julio Rozas <ref name="Vieira and Rozas">DOI: 10.1093/gbe/evr033</ref>]]

==The molecular basis of chemical communication==
The sense of smell, [http://en.wikipedia.org/wiki/Olfaction Olfaction] is a primary sense in nature. It plays a significant role in behaviors which are crucial for the organism survival: food searching, host and mating selection, and avoiding predators and pathogens <ref name="kaupp">DOI: 10.1038/nrn2789</ref>.

In both [http://en.wikipedia.org/wiki/Arthropod arthropods] and [http://en.wikipedia.org/wiki/Vertebrate vertebrates] the detection of volatiles is completed by a complicated process which is mediated by soluble as well as transmembrane proteins <ref name="pelosi">DOI: 10.3389/fphys.2014.00320</ref>.
It should be mentioned that the detection of [http://en.wikipedia.org/wiki/Pheromone pheromones] is also vital to microorganisms, as it regulates gene expression in what is termed [http://en.wikipedia.org/wiki/Quorum_sensing “quorum sensing”].
In arthropods, most of what is known on chemosensory communication is based on insects' research. The process begins when a volatile (mostly a small [http://en.wikipedia.org/wiki/Hydrophobe hydrophobic] molecule) enters the chemosensilla lymph of an insect, or the mucus of a vertebrate in the nasal cavity ([[fig 1]]). Both mediums are abundant in soluble proteins which binds to the hydrophobic molecules, solubilizes and carries it to the [http://en.wikipedia.org/wiki/Chemoreceptor chemoreceptors] on the dendritic membrane of the olfactory receptor neuron <ref name="kaupp" /><ref>Vogt RG (2005) Molecular basis of pheromone detection in insects. Comprehensive Insect Physiology, Biochemistry, Pharmacology and Molecular Biology, eds Gilbert LI, Iatro K, Gills S (Elsevier, London), Vol 3, pp 753–804.</ref>.The chemical signal is there by translated into an electrical signal which can cause an immediate response, or further elaborate with other signals in the insect's mushroom bodies or vertebrate's brain ([[fig 2]])<ref>doi: 10.3389/fncel.2012.00048</ref><ref>doi: 10.1146/annurev-ento-120811-153635</ref>.

== What is the differences and similarities between Arthropods and Vertebrates? ==

Though functionally similar, receptors as well as soluble proteins are structurally and genetically unrelated in insects and vertebrates (see [[fig 3]] for the putative evolution of priteins involved in chemosensory system).

*'''Receptors'''
Most of the vertebrates' chemosensory receptors are metabotropic and belong to the [[G protein-coupled receptors]]. Once the volatile binds to the receptor it initiates intracellular signal transduction <ref>doi: 10.1016/S0167-4838(00)00167-9</ref>. On the other hand, arthropods' and insects' chemoreceptors are composed of two subunits: [http://en.wikipedia.org/wiki/Olfactory_receptor Receptor] and [http://en.wikipedia.org/wiki/Co-receptor Co-receptor] that upon interaction with the volatile or the complex of volatile-soluble protein, are activated and serve as an [http://en.wikipedia.org/wiki/Ion_channel ion channel]. The opening of the ion channel changes the [http://en.wikipedia.org/wiki/Membrane_potential membrane potential], and starts the inter-cellular signal transduction<ref>Vogt RG (2005) Molecular basis of pheromone detection in insects. Comprehensive Insect Physiology, Biochemistry, Pharmacology and Molecular Biology, eds Gilbert LI, Iatro K, Gills S (Elsevier, London), Vol 3, pp 753–804.</ref>.[[Image:Chemoreceptors-insects.jpg|thumb|center|upright=2.5|Figure 4: Types of insect receptors. Figure 1 from Kaupp (2010), used with permission of Prof. U. Benjamin Kaupp.]]

*'''Soluble proteins'''
These proteins which are concentrated in the sensillar lymph, solubilize and carry the volatile molecules to the receptor.
There are two main known types of soluble proteins that are involved in arthropods' chemical communication: '''[http://proteopedia.org/w/Odorant_binding_protein Odorant binding proteins –OBPs]''','''[http://proteopedia.org/wiki/index.php/Chemosensory_protein Chemosensory protein-CSP]''' ([[fig 5]]). Though bearing the same name and participating in the same function, OBP of vertebrates and arthropods are two distinct families with completely different structure and origin<ref name="pelosi" />. Arthropods' OBP are composed of alpha helices, while vertebrates' OBP belong to the [http://en.wikipedia.org/wiki/Lipocalin Lipocalins] super family and have a beta-barrel structure (for structure comparison, see [[table 1]] and [[fig 5]]). Recently, another family of protein has been suggested to play a role in ant chemical communication, '''[https://www.wikigenes.org/e/gene/e/10577.html Niemann-Pick type C2 protein-NPC2]''' <ref>DOI: 10.1073/pnas.1323928111</ref>.
[[Image:Fig 3 soluble proteins.png|thumb|center|upright=3|Figure 5. (a) An example for vertebrate's OBP-a pig OBP, PDB:[[1e06]]; (b) An example for insect's OBP- ''Bombyx mori'' PBP, PDB:[[1dqe]]; (c) An example for insect's CSP-''Mamestra brassicae'' CSP2 PDB:[[1n8u]]]]
[[Image:Soluble proteins table.png|thumb|center|upright=2|Table 1. Summation of the main structure properties of soluble proteins types]]

==Types of Soluble proteins in arthropods==
<StructureSection load='1n8u' size='340' side='right' caption='''Mamestra brassicae'' CSP2 PDB:[[1n8u]]' scene=''>
*'''OBP'''
''Drosophila melanogaster'' <scene name='61/614066/Lush/1'>LUSH</scene><ref>doi: m10.1016/j.cell.2008.04.046</ref>.

*'''CSP'''
''Mamestra brassicae'' <scene name='61/614066/Mamestra_brassicae_csp/1'>chemosensory protein</scene> in complex with its ligand bromo-dodecanol.

*'''NPC2'''
Proposed soluble protein in Camponatus ''japonicus antennae'', bears <scene name='61/614066/Resid_in_the_cavity_gate/1'>6 consereved residues at the gate of the cavity</scene>
</StructureSection>

== See also ==
*[[Odorant_binding_protein_3D_structures]]
*For comprehensive explanation about quorum sensing please turn to Fuqua et al. (2001) <ref>DOI: 10.1146/annurev.genet.35.102401.090913 </ref>.
*for more inforamtion about the protein-ligand interaction, you may go to [[Odorant binding protein]].
== References ==
<references/>

Chemical communication in arthropods

2015-01-27T12:39:49Z

Nurit Eliash:

[[Image:Sensilla.png|thumb|upright=1.5|Figure 1: Vertebrate (a), and insect (b) sensilla. Figure 1 from Kaupp (2010), used with permission of Prof. U. Benjamin Kaupp.]]
[[Image:Signal trunsdution - Sanchez 2009.jpg|thumb|right|upright=2|Figure 2.(a) Schematic representation of the general structure of an insect olfactory hair; (b) The first molecular steps of the insect chemosensory signaling transduction pathway. Figure 1 from Sánchez-Gracia et al.(2009)<ref>doi: 10.1038/hdy.2009.55</ref>, used with permission of Prof. Sa´nchez-Gracia.]]
[[Image:Vieira and Rozas 2011 fig7.JPG|thumb|upright=1.5|Figure 3. The evolution of the Chemosensory System. Blue boxes represent the aquatic lifestyle. Right: Presence or absence of the chemosensory gene families in extant species. Branch lengths are not to scale. Figure 7 from Vieira and Rozas (2011), used with permission of Prof Julio Rozas <ref name="Vieira and Rozas">DOI: 10.1093/gbe/evr033</ref>]]

==The molecular basis of chemical communication==
The sense of smell, [http://en.wikipedia.org/wiki/Olfaction Olfaction] is a primary sense in nature. It plays a significant role in behaviors which are crucial for the organism survival: food searching, host and mating selection, and avoiding predators and pathogens <ref name="kaupp">DOI: 10.1038/nrn2789</ref>.

In both [http://en.wikipedia.org/wiki/Arthropod arthropods] and [http://en.wikipedia.org/wiki/Vertebrate vertebrates] the detection of volatiles is completed by a complicated process which is mediated by soluble as well as transmembrane proteins <ref name="pelosi">DOI: 10.3389/fphys.2014.00320</ref>.
It should be mentioned that the detection of [http://en.wikipedia.org/wiki/Pheromone pheromones] is also vital to microorganisms, as it regulates gene expression in what is termed [http://en.wikipedia.org/wiki/Quorum_sensing “quorum sensing”].
In arthropods, most of what is known on chemosensory communication is based on insects' research. The process begins when a volatile (mostly a small [http://en.wikipedia.org/wiki/Hydrophobe hydrophobic] molecule) enters the chemosensilla lymph of an insect, or the mucus of a vertebrate in the nasal cavity (fig 1). Both mediums are abundant in soluble proteins which binds to the hydrophobic molecules, solubilizes and carries it to the [http://en.wikipedia.org/wiki/Chemoreceptor chemoreceptors] on the dendritic membrane of the olfactory receptor neuron <ref name="kaupp" /><ref>Vogt RG (2005) Molecular basis of pheromone detection in insects. Comprehensive Insect Physiology, Biochemistry, Pharmacology and Molecular Biology, eds Gilbert LI, Iatro K, Gills S (Elsevier, London), Vol 3, pp 753–804.</ref>.The chemical signal is there by translated into an electrical signal which can cause an immediate response, or further elaborate with other signals in the insect's mushroom bodies or vertebrate's brain (fig 2)<ref>doi: 10.3389/fncel.2012.00048</ref><ref>doi: 10.1146/annurev-ento-120811-153635</ref>.

== What is the differences and similarities between Arthropods and Vertebrates? ==

Though functionally similar, receptors as well as soluble proteins are structurally and genetically unrelated in insects and vertebrates (see [[figure 3]] for the putative evolution of priteins involved in chemosensory system).

*'''Receptors'''
Most of the vertebrates' chemosensory receptors are metabotropic and belong to the [[G protein-coupled receptors]]. Once the volatile binds to the receptor it initiates intracellular signal transduction <ref>doi: 10.1016/S0167-4838(00)00167-9</ref>. On the other hand, arthropods' and insects' chemoreceptors are composed of two subunits: [http://en.wikipedia.org/wiki/Olfactory_receptor Receptor] and [http://en.wikipedia.org/wiki/Co-receptor Co-receptor] that upon interaction with the volatile or the complex of volatile-soluble protein, are activated and serve as an [http://en.wikipedia.org/wiki/Ion_channel ion channel]. The opening of the ion channel changes the [http://en.wikipedia.org/wiki/Membrane_potential membrane potential], and starts the inter-cellular signal transduction<ref>Vogt RG (2005) Molecular basis of pheromone detection in insects. Comprehensive Insect Physiology, Biochemistry, Pharmacology and Molecular Biology, eds Gilbert LI, Iatro K, Gills S (Elsevier, London), Vol 3, pp 753–804.</ref>.[[Image:Chemoreceptors-insects.jpg|thumb|center|upright=2.5|Figure 2: Types of insect receptors. Figure 1 from Kaupp (2010), used with permission of Prof. U. Benjamin Kaupp.]]

*'''Soluble proteins'''
These proteins which are concentrated in the sensillar lymph, solubilize and carry the volatile molecules to the receptor.
There are two main known types of soluble proteins that are involved in arthropods' chemical communication: '''[http://proteopedia.org/w/Odorant_binding_protein Odorant binding proteins –OBPs]''','''[http://proteopedia.org/wiki/index.php/Chemosensory_protein Chemosensory protein-CSP]''' (fig 3). Though bearing the same name and participating in the same function, OBP of vertebrates and arthropods are two distinct families with completely different structure and origin<ref name="pelosi" />. Arthropods' OBP are composed of alpha helices, while vertebrates' OBP belong to the [http://en.wikipedia.org/wiki/Lipocalin Lipocalins] super family and have a beta-barrel structure (for structure comparison, see [[table 1]]). Recently, another family of protein has been suggested to play a role in ant chemical communication, '''[https://www.wikigenes.org/e/gene/e/10577.html Niemann-Pick type C2 protein-NPC2]''' <ref>DOI: 10.1073/pnas.1323928111</ref>.
[[Image:Fig 3 soluble proteins.png|thumb|center|upright=3|Figure 3. (a) An example for vertebrate's OBP-a pig OBP, PDB:[[1e06]]; (b) An example for insect's OBP- ''Bombyx mori'' PBP, PDB:[[1dqe]]; (c) An example for insect's CSP-''Mamestra brassicae'' CSP2 PDB:[[1n8u]]]]
[[Image:Soluble proteins table.png|thumb|center|upright=2|Table 1. Summation of the main structure properties of soluble proteins types]]

==Types of Soluble proteins in arthropods==
<StructureSection load='1n8u' size='340' side='right' caption='''Mamestra brassicae'' CSP2 PDB:[[1n8u]]' scene=''>
*'''OBP'''
''Drosophila melanogaster'' <scene name='61/614066/Lush/1'>LUSH</scene><ref>doi: m10.1016/j.cell.2008.04.046</ref>.

*'''CSP'''
''Mamestra brassicae'' <scene name='61/614066/Mamestra_brassicae_csp/1'>chemosensory protein</scene> in complex with its ligand bromo-dodecanol.

*'''NPC2'''
Proposed soluble protein in Camponatus ''japonicus antennae'', bears <scene name='61/614066/Resid_in_the_cavity_gate/1'>6 consereved residues at the gate of the cavity</scene>
</StructureSection>

== See also ==
*[[Odorant_binding_protein_3D_structures]]
*For comprehensive explanation about quorum sensing please turn to Fuqua et al. (2001) <ref>DOI: 10.1146/annurev.genet.35.102401.090913 </ref>.
*for more inforamtion about the protein-ligand interaction, you may go to [[Odorant binding protein]].
== References ==
<references/>