8wc3

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of the SEP363856-bound mTAAR1-Gs complex

Structural highlights

8wc3 is a 5 chain structure with sequence from Homo sapiens, Mus musculus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TAAR1_MOUSE Receptor for trace amines, including beta-phenylethylamine (b-PEA), p-tyramine (p-TYR), octopamine and tryptamine, with highest affinity for b-PEA and p-TYR. Unresponsive to classical biogenic amines, such as epinephrine and histamine and only partially activated by dopamine and serotonin. Trace amines are biogenic amines present in very low levels in mammalian tissues. Although some trace amines have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Trace amines are likely to be involved in a variety of physiological functions that have yet to be fully understood. The signal transduced by this receptor is mediated by the G(s)-class of G-proteins which activate adenylate cyclase.^[1]

Publication Abstract from PubMed

Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D(3.32) for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design.

Structural and signaling mechanisms of TAAR1 enabled preferential agonist design.,Shang P, Rong N, Jiang JJ, Cheng J, Zhang MH, Kang D, Qi L, Guo L, Yang GM, Liu Q, Zhou Z, Li XB, Zhu KK, Meng QB, Han X, Yan W, Kong Y, Yang L, Wang X, Lei D, Feng X, Liu X, Yu X, Wang Y, Li Q, Shao ZH, Yang F, Sun JP Cell. 2023 Nov 22;186(24):5347-5362.e24. doi: 10.1016/j.cell.2023.10.014. Epub , 2023 Nov 13. PMID:37963465^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC. Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors. Genomics. 2005 Mar;85(3):372-85. PMID:15718104 doi:10.1016/j.ygeno.2004.11.010
↑ Shang P, Rong N, Jiang JJ, Cheng J, Zhang MH, Kang D, Qi L, Guo L, Yang GM, Liu Q, Zhou Z, Li XB, Zhu KK, Meng QB, Han X, Yan W, Kong Y, Yang L, Wang X, Lei D, Feng X, Liu X, Yu X, Wang Y, Li Q, Shao ZH, Yang F, Sun JP. Structural and signaling mechanisms of TAAR1 enabled preferential agonist design. Cell. 2023 Nov 22;186(24):5347-5362.e24. PMID:37963465 doi:10.1016/j.cell.2023.10.014

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8wc3"

@@ Line 9: / Line 9: @@
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.<ref>PMID:18611381</ref>
+[https://www.uniprot.org/uniprot/TAAR1_MOUSE TAAR1_MOUSE] Receptor for trace amines, including beta-phenylethylamine (b-PEA), p-tyramine (p-TYR), octopamine and tryptamine, with highest affinity for b-PEA and p-TYR. Unresponsive to classical biogenic amines, such as epinephrine and histamine and only partially activated by dopamine and serotonin. Trace amines are biogenic amines present in very low levels in mammalian tissues. Although some trace amines have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Trace amines are likely to be involved in a variety of physiological functions that have yet to be fully understood. The signal transduced by this receptor is mediated by the G(s)-class of G-proteins which activate adenylate cyclase.<ref>PMID:15718104</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 8wc3" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Transducin 3D structures|Transducin 3D structures]]
 == References ==
 <references/>

8wc3

From Proteopedia

Current revision

Cryo-EM structure of the SEP363856-bound mTAAR1-Gs complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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