Receptor

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1 Transmembrane (cell surface) receptors
2 Intracellular receptors

Transmembrane (cell surface) receptors

Ion channel-linked (ionotropic) receptors

These receptors are typically the targets of fast neurotransmitters such as acetylcholine (nicotinic) and GABA; activation of these receptors results in changes in ion movement across a membrane.

5-HT3 receptor

The receptor is bullet-shaped and consists of 5 subunits (A-E) that form an oligomer. In the center of this pentamer of subunits is a ligand-gated ion channel full of water, which the 5 subunits enclose pseudo-symmetrically. Each subunit of the 5-HT3 receptor consists of 3 regions; the extracellular region, the transmembrane region, and the intracellular region. The is relatively large compared to the other 2 regions, and contains a short C-terminus and a larger N-terminus. The N-terminus of the extracellular region is where the ligand binding occurs, and therefore deals with the agonists and antagonists. These are located between 2 bordering subunits, assembled from 3 α-helices of 1 subunit and 3 β-strands from the other subunit. Such connection creates a binding pocket with a small, select number of residues from each subunit pointed into the binding pocket, as opposed to the large remainder of residues that are pointing from the binding pocket. This binding pocket shrinks around agonists, encapsulating them, and widens around antagonists, repulsing them. The is within the C-terminus region, and contains 4 α-helical domains within it (M1-M4) that stretch the length of this inner, transmembrane area. These 4 α-helical domains conduct the channel openings via ion selectivity, depending on both charge and size. M2, the porous domain, contains rings of charged amino acids at both its start and its , accounting for M2’s main contribution to ion selectivity. The M3 and M4 α-helices create a large with one another, thus assembling the .

Nicotinic Acetylcholine Receptors in general

The receptor is a transmembrane pentameric glycoprotein. It cylindrical in appearance by electron microscopy approximately 16nm in length and 8nm in diameter. The main ion channel is composed of a water pore that runs through the entire length of the protein. If viewed from the synaptic cleft, the protein will look like a pseudo-symmetrical rosette shown in the picture below composed of 10 different alpha and 4 different beta subunits.

Alpha-bungarotoxin is a nicotinic cholinergic antagonist that is found within the venom of Bungarus multicinctus, a South-asian snake.
Binding site of AChR
Acetylcholine Receptor and its Reaction to Cobra Venom

When cobra venom is introduced into the body is moves along the bloodstream to a diaphragm muscle. It works as a postsynaptic neurotoxin binding to the receptor as an extracellular ligand by interacting with OH group leaving the acetylcholine channel open which releases ions used in creating an action potential. There must be 5 molecules of cobra toxin (red) to block the receptor (blue) as each molecule binds with an individual alpha chain on the acetylcholine receptor. The 2nd image depicts an individual toxin binding with one chain on the receptor, both in the same color. This representation shows each molecule of the .

AMPA glutamate receptor by University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground.

Full view of the glutamate receptor shows the overall structure (amino-terminal, ligand-binding and transmembrane domains) in both (MF) and models.

Zooming in at the top of the receptor () (RCB) one can view the amino terminal domain, which is a part of the extracellular domain. This domain is implicated in receptor assembly, trafficking, and localization.

Moving toward the bottom of the receptor () (SM) one can view the transmembrane domain. Here is the same domain separated from the rest of the protein. (DM). This domain widens in response to glutamate binding allowing for positive ions to pass through the post-synaptic membrane.

This view () highlights the area where a receptor antagonist 2K200225, will bind. Close up view of the ligand binding site () (AH) of the endogenous ligand glutamate.

Glutamate receptor (GluA2)

G protein-linked (metabotropic) receptors

This is the largest family of receptors and includes the receptors for several hormones and slow transmitters (dopamine, metabotropic glutamate). They are composed of 7 transmembrane alpha helices. The loops connecting the α-helices form extracellular and intracellular domains. The binding-site for larger peptide ligands is usually located in the extracellular domain whereas the binding site for smaller non-peptide ligands is often located between the seven alpha helices and one extracellular loop. These receptors are coupled to different intracellular effector systems via G proteins

You can check out the in the window on the right. It shows the mu opioid receptor bound to a peptide ligand and a G protein . The G protein ("G" because it binds to GTP) consists of three parts A , B , and C ).

Mu Opioid Receptor Bound to a Morphinan Antagonist

In this crystal structure of the μ opioid receptor it is (β-FNA), a close relative of morphine that is bound in the pocket.

In the case of the μ-opioid receptor, the binding of an opioid signaling molecule induces a in the receptor that activates an inhibitory G-protein (Gαi/o). This results in the dissociation of the G-protein complex. The Gα subunit then inhibits adenylyl cyclase. The Gβγ subunit acts to inhibit Ca2+ channels while activing K+ channels. While much has been learned about μ-opioid receptors since their discovery in 1973, there is still much that is unknown about their structure and .

The κ-opioid receptor binds opium-type ligands

The κ-opioid receptor is a . The extracellular side is home to the proteins primary . These two units will span the length for the cell membrane to form the basis of the receptor molecule. The each subunit is attached to the other by the I, II and VIII alpha helices. This can be seen where helices I (in light blue) and helices VIII (in dark blue). This area will make up the basis for the intermembrane surface area. A distinguishing feature that separates the κ-opioid receptor from other receptors, is the large beta hairpin, , located near the main active site of the protein. It is believed that its function is to cap the active site of the receptor. Although in general, this protein is primarily composed of alpha helices, not beta sheets (Compare to here). This evidence reinforces the idea that this protein is a transmembrane protein rather than one found inside the cytosol. In general transmembrane protein are composed almost entirely of alpha helices (or beta sheets arranged in special fashion called a beta barrel), in order to have maximum stability inside the membrane. Another interesting feature of the κ-opioid receptor is the formed by Cys131 and Cys210 which is conserved across all opioid receptors. of κ-opioid receptor. The human kappa opioid receptor (hKOR) ligand binding pocket displays a unique combination of key characteristics both shared with and distinct from those in the chemokine and aminergic receptor families.

The δ-opioid receptor binds enkephalins

Opioid receptors typically have 2 big portions: the upper portion, zoomed in here with shown in indigo, that is ligand specific and recognizes a particular ligand, and the lower portion which is highly conserved amongst all receptors ^[2]. When approaches delta opioid receptor, it is distinguished by the high hydrophobic interaction between the indole group on the ligand and leucine 300 on the receptor. As it glides deeper into the binding site facilitated by the hydrophobic interaction, the hydroxyl group of the tyrosine-like phenol group hydrogen bonds with water molecules which are hydrogen bound to a critical histidine 248. This holds the ligand by having both the phenol group and histidine anchored by a water molecule. The water molecules within the binding pocket flank both the ligand and receptor, serving almost as a scaffolding on which for both components to act. Adjacent to the phenol group, the oxygen of an ether is hydrogen bound to tyrosine 129 of the receptor. On the opposite side of the binding site, Asp128 forms a salt bridge with the charged amino group on the ligand. The rest of the ligand maintains hydrophobic contact with non-polar residues of the binding site. The phenol to water interaction is a conserved interaction between many opioid receptors and their respective ligands as evidenced by many natural antagonists having a tyrosine that interacts with a water molecule in a similar fashion ^[3].

Neurotensin receptor

Like other G protein-coupled receptors, NTSR1 is composed of 3 distinct regions. An where neurotensin binds and causes a conformational change of the protein. A region containing (PDB code:4GRV) that transduce the signal from the extracellular side of the cell membrane to the intracellular side. Lastly, an intracellular region that when activated by a conformational change in the protein activates a G-protein associated with this receptor.

The in NTSR1 is located at the top of the protein (Figure 1). NTSR1 also contains an allosteric , which is located directly beneath the ligand binding pocket and the two pockets, which are separated by the residue ^[4]. NTSR1 has been mutated to exist in both and states.

CXC chemokine receptor type 4

(PDB code 3oe0).

Orexin and Orexin receptor

The through a constricted solvent-accessible channel. A ^[5].

Belsomra and Orexin receptors
Hypocretin and receptors
Human Follicle-Stimulating Hormone Complexed with its Receptor
GPR40

Like most G-protein coupled receptors, hGPR40 contains (). To obtain a crystal structure of the protein, 4 (, , , ) were made to increase the expression and thermal stability of the protein. These mutations did not significantly impact the enzyme's binding affinity with a known agonist TAK-875. (in crimson) was also added to intracellular loop 3 to aid in the formation of crystals.

While there is relatively low sequence identity between hGPR40 and peptide-binding and opioid GPCRs, they do share structural similarities such as a conserved motif on (ECL2). In addition, a conserved is formed between transmembrane helix 3 (Cys 79) and the C-terminus of ECL2 (Cys170). Compared to peptide-binding and opioid GPCRs, which have distinctive β-sheets spanning from transmembrane helix 4 to 5, hGPR40 possesses a shorter B-sheet-like region, which has low B-factors. This reflects the low mobility of the region that limits the overall flexibility of the adjacent portion of ECL2 between Leu171 and Asp175. A unique feature of hGPR40 is the presence of an additional 13 residues (Pro147 to Gly159) on ECL2, which is absent on all the other peptide/opioid receptors. These extra residues form a separate between the B-sheet-like region and transmembrane 4. Together, the auxiliary loop and ECL2 of hGPR40 function as a over the canonical binding site covering it from the central extracellular region.

The canonical binding pocket for many other GPCRs is solvent exposed and centrally located between the transmembrane helices allowing ligands to directly bind from the extracellular space. However, because acts as a roof to this canonical binding site, it inhibits ligands from entering directly from the extracellular region. Instead, the highly lipophilic nature of hGPRC40’s ligands allow it to enter a between TM3 and TM4 by moving through the lipid bilayer.

FFAs bind to hGPR40 by coordinating its free carboxyl group to 3 amino acids, , which are located close to the of hGPR40 on TM5, 6 and 7. Because of the close proximity of these residues to the extracellular domain and the dominantly hydrophobic nature of FFA’s, it is likely that ligand binding occurs close to the plane of the membrane.

The has been identified, but other binding sites were hypothesized. TAK-875 binds between transmembrane helices 3, 4, and 5 and underneath ECL2. hGPR40 has a distinct binding pocket that is established by : , , , , , , , and (all individual residues shown in chartreuse). The importance of these residues for agonist binding was determined by alanine site-directed-mutagenesis mutagenesis studies. When the substrate (an agonist) enters the binding pocket, 4 of the 8 interact directly with the carboxylate moiety of the agonist by hydrogen bonding to it. These residues include 2 key arginines in the binding pocket, Arg183 and Arg258, and 2 key tyrosine residues, Tyr91 and Tyr240. Tyr240 is especially important for binding, as mutation of Tyr240 caused an eight fold reduction in the binding affinity of TAK-875 and had a significant effect on the binding affinity (K_D) of the protein.

hGPR40 contains a highly conserved hairpin extracellular loop () is the longest and most divergent of the extracellular loops found in proteins (). The loop is accompanied by a disulfide bond () that forms between transmembrane helix 4 and the C-terminus of the ECL2 loop. In hGPR40, ECL2 has two sections: a beta sheet and an auxiliary loop. The β-sheet spans helices 4 and 5 and is shorter in hGPR40 than in other GPCRs. The ECL2 of hGPR40 also differs from that of other proteins because it contains an auxiliary loop of 13 extra residues. The entire extracellular loop has low mobility and flexibility, which allows it to act as a cap for the binding pocket. The only exception to the low flexibility is the tip of the auxiliary loop, which corresponds to residues Asp152-Asn155. This area of greater mobility allows for substrates to enter the binding site.

is a partial agonist of GPR40 and tested for the treatment of type 2 diabetes. The binding of TAK-875 to hGPR40 occurs by the ligand entering the binding site through the membrane bilayer. This membrane insertion is performed via a method similar to ligand binding to sphingosine 1-phosphate receptor 1, retinal loading of GPCR opsin, and the entry of anandamide in cannabinoid receptors, in which the block the binding from the extracellular matrix ^[6].

TAK-875 binds to the created between transmembrane (TM) domains 3-5 and the extracellular loop 2 (ECL2) of hGPR40. The ECL2 and auxiliary loop form a roof causing TAK-875 to enter through TM3 and TM4, first passing through the lipid bilayer. The carboxylate of TAK-875 is buried within a very hydrophobic region and in a complex complex involving Glu172, Ser187, Asn241, and Asn 244 from hGPR40 forming ionic and polar interactions by coordinating TAK-875 with Arg183, Arg258, Tyr91, and Tyr240.

Lysophosphatidic acid receptor

LPA₁ lies in the membrane as shown by the bound in the crystallization of LPA₁ in orange. Most (red) reside on the intracellular and extracellular areas of the receptor, while most residues positioned on the trans membrane helices inside the membrane are hydrophobic (blue). A cytochrome b (b₅₆₂RIL) protein was inserted into the 3rd intracellular loop to facilitate crystallization. The intracellular region of this membrane protein is coupled to a heterotrimeric G protein.

Three native in the extracellular region of this receptor provide fold stability. The 1st disulfide bond constrains the N terminal helix to extracellular loop (ECL) 2. The 2nd disulfide bond shapes ECL2, and the 3rd binds ECL3 to one of the transmembrane alpha helices. These disulfide bonds provide intramolecular stabilization along the extracellular region of the LPA₁ receptor, where the substrate enters into the binding pocket. The is a 6 turn α-helix and functions like a cap on the extracellular side of the protein, packing tightly against ECL1 and ECL2. The N-terminus helix also provides that interact with the ligand when bound. The extracellular region of this receptor plays a role in substrate specificity.

The biological ligand of the LPA₁ receptor receptor is lysophosphatidic acid (LPA), a phospholipid that contains a long, nonpolar tail, a phosphate head, a chiral hydroxyl group, and an ester group. This receptor provides specificity for its ligand by the amphipathic binding pocket; the positive region on the left hand side of the pocket stabilizes the LPA's phosphate group, the nonpolar region at the bottom of the binding pocket stabilizes the hydrophobic tail of LPA, and the polar region at the top of the pocket stabilize binding of the ester and hydroxyl group. The for LPA consists of both polar and nonpolar residues. residues are located on the N terminus and within the binding pocket. A also interacts with the long acyl chain of LPA. The shape and polarity of the binding pocket makes it specific for molecules with a polar head and long hydrophobic tail shaped like LPA.

Sphingosine 1-phosphate Receptor
Rhodopsin
Rhodopsin Structure and Function
Serotonin receptors, main page
3D structures of Serotonin receptors
Adrenergic receptors in general
Beta-1 Adrenergic receptor
Dobutamine: Beta-1 Adrenergic receptor, 2y00, 2y01, 6h7l
Isoprenaline: Beta-1 Adrenergic receptor, 2y03
Carmoterol: 2y02
Salbutamol: 2y04
Adrenergic receptor page.
Article Beta-2 Adrenergic Receptor by Wayne Decatur, David Canner, Dotan Shaniv, Joel L. Sussman, Michal Harel
Article Beta-2 adrenergic receptor by Joel L. Sussman, Tala Curry, Michal Harel, Jaime Prilusky
Group:SMART:A Physical Model of the beta-Adrenergic Receptor
G_s: adenylate cyclase activated, cAMP up. For G_s see Beta2 adrenergic receptor-Gs protein complex updated
Dopamine receptors 1 page
Dopamine receptors 2 page
Histamine H1 receptor
3rze - human histamine H1 receptor with an antagonist doxepin
Adenosine A2A receptor
Effect of Caffeine (Trimethylxanthine) on Human A2A Receptor
Muscarinic acetylcholine receptor
Glucose-dependent Insulinotropic Polypeptide Receptor
Glucagon receptor
Glucagon-like peptide 1 receptor
Metabotropic Glutamate Receptors
Ligand Binding N-Terminal of Metabotropic Glutamate Receptors
Metabotropic glutamate receptor 5

Kinase-linked, enzyme-linked and related receptors

Receptor tyrosine kinases

Receptor tyrosine kinases (RTKs) are part of the larger family of protein tyrosine kinases. They are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Approximately 20 different RTK classes have been identified.^[7]

RTK class I Epidermal Growth Factor Receptor family
RTK class II Insulin receptor family
RTK class III Platelet-derived growth factor receptor family
RTK class IV Vascular Endothelial Growth Factor Receptor family
RTK class V Fibroblast growth factor receptor family
RTK class VIII Hepatocyte growth factor receptor family
RTK class IX Ephrin receptor family
RTK class XIII Epithelial discoidin domain-containing receptor (DDR receptor) family
Neurotrophin: High affinity nerve growth factor receptor (or Tyrosine kinase receptor) and TrkB tyrosine kinase receptor
Insulin-like growth factor receptor

Enzyme-linked receptor

Immune receptors

Leukocyte immunoglobulin-like receptors

Leukocyte immunoglobulin-like receptor

Cytokine receptors

TNF receptor superfamily

Tumor necrosis factor receptor
- TRAIL (TNF-related apoptosis-inducing ligand) or TNF ligand superfamily 10

Colony-stimulating factor receptor

Type I cytokine receptors

Type II cytokine receptors

Interferon receptors

Interleukin receptors

Interleukin receptor

Interleukin-20 receptor:

Flexible regions govern promiscuous binding of IL-24 to receptors IL-20R1 and IL-22R1

Chemokine receptors, two of which acting as binding proteins for HIV (CXCR4 and CCR5). They are G protein-coupled receptors

T-cell receptors

TGF-beta receptor

TGF-beta receptor

LDL receptor

LDL receptor

Transferrin receptor

Transferrin receptor

Intracellular receptors

Signal recognition particle receptor

Signal recognition particle receptor

Receptor for activated C kinase 1

Receptor for activated protein kinase C 1

Nuclear receptors

Nuclear receptors
Thyroid hormone receptor
Retinoic acid receptor
RA Mediated T-reg Differentiation; Retinoic acid acts as the ligand for the Retinoic Acid Receptor-α (RARα) / Retinoid X Receptor-α (RXRα) heterodimer
PPAR-gamma
Pioglitazone is a selective agonist for Peroxisome Proliferator-Activated Receptor Gamma
Liver X receptor
Bile acid receptor
Vitamin D receptor
Pregnane X receptor
Retinoid X receptor
Estrogen receptor
Ivan Koutsopatriy estrogen receptor
Estrogen receptor#Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of SERMs ^[8]
Estrogen receptor#Estrogen receptor α complexed with raloxifene and a corepressor peptide
Tamoxifen and the Estrogen receptor
Student Project 10 for UMass Chemistry 423 Spring 2015
Estrogen-related receptor
Glucocorticoid receptor
Mineralocorticoid receptor
Progesterone receptor
Androgen receptor
Liver receptor homolog-1?

Endoplasmic reticulum/Sarcoplasmic reticulum receptors

Ligand-gated Calcium channels

Inositol 1,4,5-Trisphosphate Receptor

Ryanodine receptor

SEE ALSO:

References

↑ De Rienzo F, Moura Barbosa AJ, Perez MA, Fernandes PA, Ramos MJ, Menziani MC. The extracellular subunit interface of the 5-HT(3) receptors: a computational alanine scanning mutagenesis study. J Biomol Struct Dyn. 2012 Jul;30(3):280-98. Epub 2012 Jun 12. PMID:22694192 doi:10.1080/07391102.2012.680029
↑ Granier S, Manglik A, Kruse AC, Kobilka TS, Thian FS, Weis WI, Kobilka BK. Structure of the delta-opioid receptor bound to naltrindole. Nature. 2012 May 16;485(7398):400-4. doi: 10.1038/nature11111. PMID:22596164 doi:10.1038/nature11111
↑ Granier S, Manglik A, Kruse AC, Kobilka TS, Thian FS, Weis WI, Kobilka BK. Structure of the delta-opioid receptor bound to naltrindole. Nature. 2012 May 16;485(7398):400-4. doi: 10.1038/nature11111. PMID:22596164 doi:10.1038/nature11111
↑ Krumm BE, White JF, Shah P, Grisshammer R. Structural prerequisites for G-protein activation by the neurotensin receptor. Nat Commun. 2015 Jul 24;6:7895. doi: 10.1038/ncomms8895. PMID:26205105 doi:http://dx.doi.org/10.1038/ncomms8895
↑ Yin J, Mobarec JC, Kolb P, Rosenbaum DM. Crystal structure of the human OX orexin receptor bound to the insomnia drug suvorexant. Nature. 2014 Dec 22. doi: 10.1038/nature14035. PMID:25533960 doi:http://dx.doi.org/10.1038/nature14035
↑ Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, Reinhart G, Desale H, Clemons B, Cahalan SM, Schuerer SC, Sanna MG, Han GW, Kuhn P, Rosen H, Stevens RC. Crystal structure of a lipid G protein-coupled receptor. Science. 2012 Feb 17;335(6070):851-5. PMID:22344443 doi:10.1126/science.1215904
↑ Segaliny AI, Tellez-Gabriel M, Heymann MF, Heymann D. Receptor tyrosine kinases: Characterisation, mechanism of action and therapeutic interests for bone cancers. J Bone Oncol. 2015 Jan 23;4(1):1-12. doi: 10.1016/j.jbo.2015.01.001. eCollection , 2015 Mar. PMID:26579483 doi:http://dx.doi.org/10.1016/j.jbo.2015.01.001
↑ Li MJ, Greenblatt HM, Dym O, Albeck S, Pais A, Gunanathan C, Milstein D, Degani H, Sussman JL. Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of selective estrogen receptor modulators. J Med Chem. 2011 Apr 7. PMID:21473635 doi:10.1021/jm200192y

Proteopedia Page Contributors and Editors (what is this?)

Alexander Berchansky

Retrieved from "http://52.214.119.220/wiki/index.php/Receptor"

@@ Line 12: / Line 12: @@
 '''5-HT3 receptor'''
-The <scene name='71/716487/Default/1'>5-HT3 </scene> receptor is bullet-shaped and consists of 5 subunits (A-E) that form an oligomer. In the center of this pentamer of subunits is a ligand-gated ion channel full of water, which the 5 subunits enclose pseudo-symmetrically. Each subunit of the 5-HT3 receptor consists of 3 regions; the extracellular region, the transmembrane region, and the intracellular region.
+The <scene name='71/716487/Default/1'>5-HT3 </scene> receptor is bullet-shaped and consists of 5 subunits (A-E) that form an oligomer. In the center of this pentamer of subunits is a ligand-gated ion channel full of water, which the 5 subunits enclose pseudo-symmetrically. Each subunit of the 5-HT3 receptor consists of 3 regions; the extracellular region, the transmembrane region, and the intracellular region. The <scene name='71/716487/Extracellular_region/1'>extracellular region</scene> is relatively large compared to the other 2 regions, and contains a short C-terminus and a larger N-terminus. The N-terminus of the extracellular region is where the ligand binding occurs, and therefore deals with the agonists and antagonists. These <scene name='71/716487/Binding_site/4'>binding sites</scene> are located between 2 bordering subunits, assembled from 3 α-helices of 1 subunit and 3 β-strands from the other subunit. Such connection creates a binding pocket with a small, select number of residues from each subunit pointed into the binding pocket, as opposed to the large remainder of residues that are pointing <scene name='71/716487/Default/11'> away</scene> from the binding pocket. This binding pocket shrinks around agonists, encapsulating them, and widens around antagonists, repulsing them. The <scene name='71/716487/Default/5'>transmembrane region</scene> is within the C-terminus region, and contains 4 α-helical domains within it (M1-M4) that stretch the length of this inner, transmembrane area. These 4 α-helical domains conduct the channel openings via ion selectivity, depending on both charge and size. M2, the porous domain, contains rings of charged amino acids at both its start and its <scene name='71/716487/Default/10'>end</scene>, accounting for M2’s main contribution to ion selectivity. The M3 and M4 α-helices create a large <scene name='71/716487/Default/6'>loop</scene> with one another, thus assembling the <scene name='71/716487/Default/7'>intracellular region</scene>.
-The <scene name='71/716487/Extracellular_region/1'>extracellular region</scene> is relatively large compared to the other 2 regions, and contains a short C-terminus and a larger N-terminus. The N-terminus of the extracellular region is where the ligand binding occurs, and therefore deals with the agonists and antagonists.
-These <scene name='71/716487/Binding_site/4'>binding sites</scene> are located between 2 bordering subunits, assembled from 3 α-helices of 1 subunit and 3 β-strands from the other subunit. Such connection creates a binding pocket with a small, select number of residues from each subunit pointed into the binding pocket, as opposed to the large remainder of residues that are pointing <scene name='71/716487/Default/11'> away</scene> from the binding pocket. This binding pocket shrinks around agonists, encapsulating them, and widens around antagonists, repulsing them.
-The <scene name='71/716487/Default/5'>transmembrane region</scene> is within the C-terminus region, and contains 4 α-helical domains within it (M1-M4) that stretch the length of this inner, transmembrane area. These 4 α-helical domains conduct the channel openings via ion selectivity, depending on both charge and size. M2, the porous domain, contains rings of charged amino acids at both its start and its <scene name='71/716487/Default/10'>end</scene>, accounting for M2’s main contribution to ion selectivity. The M3 and M4 α-helices create a large <scene name='71/716487/Default/6'> loop</scene> with one another, thus assembling the <scene name='71/716487/Default/7'>intracellular region</scene>.
 *[[Nicotinic Acetylcholine Receptor|Nicotinic Acetylcholine Receptors in general]]
@@ Line 29: / Line 23: @@
 *[[Binding site of AChR]]
 *[[Acetylcholine Receptor and its Reaction to Cobra Venom]]
-When cobra venom is introduced into the body is moves along the bloodstream to a diaphragm muscle. It works as a postsynaptic neurotoxin binding to the receptor as an extracellular ligand by interacting with OH group leaving the acetylcholine channel open which releases ions used in creating an action potential. There must be 5 molecules of cobra toxin (red) to block the receptor (blue) as each molecule binds with an individual alpha chain on the acetylcholine receptor. This molecule was generated by overlaying the receptor and venom using Swiss PDB viewer magic fit. The second image depicts an individual toxin binding with one chain on the receptor, both in the same color.
+When cobra venom is introduced into the body is moves along the bloodstream to a diaphragm muscle. It works as a postsynaptic neurotoxin binding to the receptor as an extracellular ligand by interacting with OH group leaving the acetylcholine channel open which releases ions used in creating an action potential. There must be 5 molecules of cobra toxin (red) to block the receptor (blue) as each molecule binds with an individual alpha chain on the acetylcholine receptor. The 2nd image depicts an individual toxin binding with one chain on the receptor, both in the same color.
 <scene name='77/778333/Cobra_snake_venom/3'>Cobra Venom Interaction with Acetylcholine Receptor</scene>
 This representation shows each molecule of the <scene name='77/778333/Venom_receptor_piece/1'>Cobra toxin binding to one chain of the receptor</scene>.
@@ Line 40: / Line 34: @@
 Moving toward the bottom of the receptor (<scene name='Molecular_Playground/Glutamate_Receptor/Transmembrane_domains/5'>Transmembrane Domain</scene>) (SM) one can view the transmembrane domain. Here is the same domain separated from the rest of the protein.<scene name='Molecular_Playground/Glutamate_Receptor/Transmembrane_domains_pore2/1'>Transmembrane Domain</scene> (DM). This domain widens in response to glutamate binding allowing for positive ions to pass through the post-synaptic membrane.
-This view (<scene name='Molecular_Playground/Glutamate_Receptor/Glu_antagoinist/2'>receptor antagonist</scene>) highlights the area where a receptor antagonist, 2K200225, will bind.
+This view (<scene name='Molecular_Playground/Glutamate_Receptor/Glu_antagoinist/2'>receptor antagonist</scene>) highlights the area where a receptor antagonist 2K200225, will bind. Close up view of the ligand binding site (<scene name='Molecular_Playground/Glutamate_Receptor/Glu_agonist_/2'>Glutamate Binding</scene>) (AH) of the endogenous ligand glutamate.
-Close up view of the ligand binding site (<scene name='Molecular_Playground/Glutamate_Receptor/Glu_agonist_/2'>Glutamate Binding</scene>) (AH) of the endogenous ligand glutamate.
 *[[Glutamate receptor (GluA2)]]
 ==G protein-linked (metabotropic) receptors==
-This is the largest family of receptors and includes the receptors for several hormones and slow transmitters (dopamine, metabotropic glutamate). They are composed of 7 transmembrane alpha helices. The loops connecting the alpha helices form extracellular and intracellular domains. The binding-site for larger peptide ligands is usually located in the extracellular domain whereas the binding site for smaller non-peptide ligands is often located between the seven alpha helices and one extracellular loop. These receptors are coupled to different intracellular effector systems via G proteins
+This is the largest family of receptors and includes the receptors for several hormones and slow transmitters (dopamine, metabotropic glutamate). They are composed of 7 transmembrane alpha helices. The loops connecting the α-helices form extracellular and intracellular domains. The binding-site for larger peptide ligands is usually located in the extracellular domain whereas the binding site for smaller non-peptide ligands is often located between the seven alpha helices and one extracellular loop. These receptors are coupled to different intracellular effector systems via G proteins
 *[[G protein-coupled receptor|G protein-coupled receptors]]
 *[[Tutorial: The opioid receptor, a molecular switch]]
@@ Line 89: / Line 81: @@
 *[[Student Project 3 for UMass Chemistry 423 Spring 2015|The '''κ-opioid receptor''' binds opium-type ligands]]
-The κ-opioid receptor is a <scene name='48/483884/K_or_general/1'>dimer composed of two identical subunits</scene>. The extracellular side is home to the proteins primary <scene name='48/483884/K_or_binding_general/2'>active site</scene>. These two units will span the length for the cell membrane to form the basis of the receptor molecule.  The each subunit is attached to the other by the I, II and VIII alpha helices. This can be seen <scene name='48/483884/K_or_dimmer_assembly/1'>here</scene> where helices I (in light blue) and helices VIII (in dark blue).  This area will make up the basis for the intermembrane surface area.  A distinguishing feature that separates the κ-opioid receptor from other receptors, is the large beta hairpin, <scene name='48/483884/K_or_beta_sheet/3'>ECL2</scene>, located near the main active site of the protein.  It is believed that its function is to cap the active site of the receptor.  Although in general, this protein is primarily composed of alpha helices, not beta sheets (Compare <scene name='48/483884/K_or_beta_sheet/1'>beta sheet</scene> to <scene name='48/483884/K_or_alpha/1'>alpha helices</scene> here). This evidence reinforces the idea that this protein is a transmembrane protein rather than one found inside the cytosol.  In general transmembrane protein are composed almost entirely of alpha helices (or beta sheets arranged in special fashion called a beta barrel), in order to have maximum stability inside the membrane.  Another interesting feature of the κ-opioid receptor is the <scene name='48/483884/K_or_disulfide_bond/1'>disulfide bond </scene> formed by Cys131 and Cys210 which is conserved across all opioid receptors.
+The κ-opioid receptor is a <scene name='48/483884/K_or_general/1'>dimer composed of two identical subunits</scene>. The extracellular side is home to the proteins primary <scene name='48/483884/K_or_binding_general/2'>active site</scene>. These two units will span the length for the cell membrane to form the basis of the receptor molecule.  The each subunit is attached to the other by the I, II and VIII alpha helices. This can be seen <scene name='48/483884/K_or_dimmer_assembly/1'>here</scene> where helices I (in light blue) and helices VIII (in dark blue).  This area will make up the basis for the intermembrane surface area. A distinguishing feature that separates the κ-opioid receptor from other receptors, is the large beta hairpin, <scene name='48/483884/K_or_beta_sheet/3'>ECL2</scene>, located near the main active site of the protein.  It is believed that its function is to cap the active site of the receptor.  Although in general, this protein is primarily composed of alpha helices, not beta sheets (Compare <scene name='48/483884/K_or_beta_sheet/1'>beta sheet</scene> to <scene name='48/483884/K_or_alpha/1'>alpha helices</scene> here). This evidence reinforces the idea that this protein is a transmembrane protein rather than one found inside the cytosol.  In general transmembrane protein are composed almost entirely of alpha helices (or beta sheets arranged in special fashion called a beta barrel), in order to have maximum stability inside the membrane.  Another interesting feature of the κ-opioid receptor is the <scene name='48/483884/K_or_disulfide_bond/1'>disulfide bond </scene> formed by Cys131 and Cys210 which is conserved across all opioid receptors.
 <scene name='48/483884/K_or_ligand_biding_pocket_asp/1'>Active site</scene> of κ-opioid receptor. The human kappa opioid receptor (hKOR) ligand binding pocket displays a unique combination of key characteristics both shared with and distinct from those in the chemokine and aminergic receptor families.
 *[[Delta opioid receptor|The '''δ-opioid receptor''' binds enkephalins]]
-Opioid receptors typically have two big portions: the upper portion, zoomed in here with <scene name='71/715422/Sceneactivesite/1'>active site</scene> shown in indigo, that is ligand specific and recognizes a particular ligand, and the lower portion which is highly conserved amongst all receptors <ref>doi: 10.1038/nature11111</ref>. When <scene name='71/715422/Sceneligand/1'>Naltrindole</scene> approaches delta opioid receptor, it is distinguished by the high hydrophobic interaction between the indole group on the ligand and leucine 300 on the receptor. As it glides deeper into the binding site facilitated by the hydrophobic interaction, the hydroxyl group of the tyrosine-like phenol group hydrogen bonds with water molecules which are hydrogen bound to a critical histidine 248. This holds the ligand by having both the phenol group and histidine anchored by a water molecule. The water molecules within the binding pocket flank both the ligand and receptor, serving almost as a scaffolding on which for both components to act.  Adjacent to the phenol group, the oxygen of an ether is hydrogen bound to tyrosine 129 of the receptor. On the opposite side of the binding site, Asp128 forms a salt bridge with the charged amino group on the ligand. The rest of the ligand maintains hydrophobic contact with non-polar residues of the binding site. The phenol to water interaction is a conserved interaction between many opioid receptors and their respective ligands as evidenced by many natural antagonists having a tyrosine that interacts with a water molecule in a similar fashion <ref>doi: 10.1038/nature11111</ref>.
+Opioid receptors typically have 2 big portions: the upper portion, zoomed in here with <scene name='71/715422/Sceneactivesite/1'>active site</scene> shown in indigo, that is ligand specific and recognizes a particular ligand, and the lower portion which is highly conserved amongst all receptors <ref>doi: 10.1038/nature11111</ref>. When <scene name='71/715422/Sceneligand/1'>Naltrindole</scene> approaches delta opioid receptor, it is distinguished by the high hydrophobic interaction between the indole group on the ligand and leucine 300 on the receptor. As it glides deeper into the binding site facilitated by the hydrophobic interaction, the hydroxyl group of the tyrosine-like phenol group hydrogen bonds with water molecules which are hydrogen bound to a critical histidine 248. This holds the ligand by having both the phenol group and histidine anchored by a water molecule. The water molecules within the binding pocket flank both the ligand and receptor, serving almost as a scaffolding on which for both components to act.  Adjacent to the phenol group, the oxygen of an ether is hydrogen bound to tyrosine 129 of the receptor. On the opposite side of the binding site, Asp128 forms a salt bridge with the charged amino group on the ligand. The rest of the ligand maintains hydrophobic contact with non-polar residues of the binding site. The phenol to water interaction is a conserved interaction between many opioid receptors and their respective ligands as evidenced by many natural antagonists having a tyrosine that interacts with a water molecule in a similar fashion <ref>doi: 10.1038/nature11111</ref>.
 *[[Neurotensin receptor]]