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Histamine H1 receptor

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==Histamine H1 Receptor==
==Histamine H1 Receptor==
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<StructureSection load='3RZE' size='340' side='right' caption='Histamine H1 receptor with an antagonist doxepin, lipid and phosphate (PDB code [[3rze]])' scene=''>
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<StructureSection load='3RZE' size='340' side='right' caption='Histamine H1 receptor with an antagonist doxepin, lipid and phosphate (PDB code [[3rze]])' scene='78/784820/2ndary_structure_color/1'>
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Allergy symptoms are mostly caused by the release of histamine in response to allergens. The binding of histamine to the extracellular portion of the '''H1 receptor''' triggers a structural change of the transmembrane portion, leading to a change in the C terminal area. This c terminal region interacts with G proteins, leading to the activation of the Gq signalling pathway, which triggers allergy symptoms like itchy eyes and runny noses. Many allergy drugs are anti-histamines, in that they bind to the histamine receptor but do not cause the conformational change that leads to a response.
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Allergy symptoms are mostly caused by the release of histamine in response to allergens. The binding of histamine to the extracellular portion of the '''H1 receptor''' triggers a structural change of the transmembrane portion, leading to a change in the C terminal area. This c terminal region interacts with G proteins, leading to the activation of the Gq signalling pathway, which triggers allergy symptoms like itchy eyes and runny noses. Many allergy drugs are anti-histamines, in that they bind to the histamine receptor but do not cause the conformational change that leads to a response. See also [[Receptor]].
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The structure of the H1 histamine receptor bound to an antihistamine, doxepin was published in 2011 <ref>PMID:21697825</ref>. A <scene name='78/784820/N_to_c_rainbow/1'>N-->C rainbow</scene> view colors the N terminus blue and the C terminus red, with the intervening segments paralleling the rainbow (blue, green, yellow, orange, red). This image is oriented with the transmembrane section at the top and the cytosolic portion below. The <scene name='78/784820/Hydrophobic/2'>hydrophobic residues</scene> are shown in grey, while hydrophilic amino acids are shown in purple.
The structure of the H1 histamine receptor bound to an antihistamine, doxepin was published in 2011 <ref>PMID:21697825</ref>. A <scene name='78/784820/N_to_c_rainbow/1'>N-->C rainbow</scene> view colors the N terminus blue and the C terminus red, with the intervening segments paralleling the rainbow (blue, green, yellow, orange, red). This image is oriented with the transmembrane section at the top and the cytosolic portion below. The <scene name='78/784820/Hydrophobic/2'>hydrophobic residues</scene> are shown in grey, while hydrophilic amino acids are shown in purple.
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<scene name='78/784820/Doxepin/3'>Doxepin</scene> was originally made as a tricyclic antidepressant, but it also is a potent antihistamine <ref>PMID: 39202</ref> binds among the transmembrane alpha helices. Binding is stabilized by a number of <scene name='78/784820/Interacting_amino_acids/4'>interactions with amino acids</scene>. Like many G protein coupled receptors, the bottom of the binding pocket contains a conserved <scene name='78/784820/Trp_428/1'>tryptophan</scene> residue. Interestingly, second generation antihistamines take advantage of an anion binding site formed by <scene name='78/784820/Lys/2'>two lysine residues</scene>; in this structure, they interact with a phosphate.
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<scene name='78/784820/Doxepin_ball_stick/1'>Doxepin</scene> was originally made as a tricyclic antidepressant, but it also is a potent antihistamine <ref>PMID: 39202</ref> binds among the transmembrane alpha helices. Binding is stabilized by a number of <scene name='78/784820/Interacting_amino_acids/4'>interactions with amino acids</scene>. Like many G protein coupled receptors, the bottom of the binding pocket contains a conserved <scene name='78/784820/Trp_428/1'>tryptophan</scene> residue. Interestingly, second generation antihistamines take advantage of an anion binding site formed by <scene name='78/784820/Lys/2'>two lysine residues</scene>; in this structure, they interact with a phosphate.
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Like other [[G protein-coupled receptor]]s, the Histamine H1 Receptor contains a <scene name='78/784820/Dry_motif/1'>conserved DRY</scene> (aspartate (D), arginine (R), tyrosine (Y)) motif in the seven helix transmembrane surface near the cytosolic face. In some G protein receptors, an "ionic lock" interaction between the asparate and arginine in this motif stabilizes the inactive state<ref>PMID:17192495</ref>; however, in the Histamine H1 receptor, Arginine 125 forms a hydrogen bond with <scene name='78/784820/Arg125_gln_416_salt_bridge/1'>glutamine 416</scene>, which stabilizes the inactive state.
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Like other [[G protein-coupled receptor]]s, the Histamine H1 Receptor contains a <scene name='78/784820/Dry_motif/1'>conserved DRY</scene> (aspartate (D), arginine (R), tyrosine (Y)) motif in the seven helix transmembrane surface near <scene name='78/784820/Dry_motif/4'>the cytosolic face</scene>. In some G protein receptors, an "ionic lock" interaction between the asparate and arginine in this motif stabilizes the inactive state<ref>PMID:17192495</ref>; however, in the Histamine H1 receptor, Arginine 125 forms a hydrogen bond with <scene name='78/784820/Arg125_gln_416_salt_bridge/1'>glutamine 416</scene>, which stabilizes the inactive state.
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See also:
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* [[G protein-coupled receptor]]
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*[[Receptor]]
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*[[Transmembrane (cell surface) receptors]]
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*[[Neurotransmitters]]
</StructureSection>
</StructureSection>
==3D structures of histamine H1 receptor==
==3D structures of histamine H1 receptor==
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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[[3rze]] - HHR + doxepin + lipid + phosphate - human<br />
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[[3rze]] - hHHR + doxepin + lipid + phosphate - human<br />
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[[7dfl]] - hHHR + guanine nucleotide-binding protein + scFv + histamine - Cryo EM<br />
== References ==
== References ==
<references/>
<references/>

Current revision

Histamine H1 Receptor

Histamine H1 receptor with an antagonist doxepin, lipid and phosphate (PDB code 3rze)

Drag the structure with the mouse to rotate

3D structures of histamine H1 receptor

Updated on 09-April-2023

3rze - hHHR + doxepin + lipid + phosphate - human
7dfl - hHHR + guanine nucleotide-binding protein + scFv + histamine - Cryo EM

References

  1. ↑ Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S. Structure of the human histamine H1 receptor complex with doxepin. Nature. 2011 Jun 22;475(7354):65-70. doi: 10.1038/nature10236. PMID:21697825 doi:10.1038/nature10236
  2. ↑ Richelson E. Tricyclic antidepressants and histamine H1 receptors. Mayo Clin Proc. 1979 Oct;54(10):669-74. PMID:39202
  3. ↑ Rovati GE, Capra V, Neubig RR. The highly conserved DRY motif of class A G protein-coupled receptors: beyond the ground state. Mol Pharmacol. 2007 Apr;71(4):959-64. doi: 10.1124/mol.106.029470. Epub 2006 Dec , 27. PMID:17192495 doi:http://dx.doi.org/10.1124/mol.106.029470

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