Transmembrane (cell surface) receptors
See also Membrane proteins.
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 .
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.
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.
This representation shows each molecule of the .
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.
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
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 [2]. NTSR1 has been mutated to exist in both and states.
(PDB code 3oe0).
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| 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 ).
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 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.
Opioid receptors typically have two 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 [3]. 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, aspartic acid 128 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 [4].
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
- Lysophosphatidic acid receptor
- Sphingosine 1-phosphate Receptor
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- 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
- Gs: adenylate cyclase activated, cAMP up. For Gs see Beta2 adrenergic receptor-Gs protein complex updated
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- 3rze - human histamine H1 receptor with an antagonist doxepin
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- Effect of Caffeine (Trimethylxanthine) on Human A2A Receptor
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- 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.[6]
Immune receptors
Leukocyte immunoglobulin-like receptors
Cytokine receptors
TNF receptor superfamily
Type I cytokine receptors
Type II cytokine receptors
Interferon receptors
Interleukin receptors
Interleukin-20 receptor:
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
LDL receptor
Transferrin receptor
Intracellular receptors
Signal recognition particle receptor
Receptor for activated C kinase 1
Nuclear receptors
Endoplasmic reticulum/Sarcoplasmic reticulum receptors
Ligand-gated Calcium channels
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