6d9h

From Proteopedia

(Difference between revisions)

Revision as of 20:52, 6 March 2020

Cryo-EM structure of the human adenosine A1 receptor-Gi2-protein complex bound to its endogenous agonist

6d9h, resolution 3.60Å

Structural highlights

6d9h is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	GNAI2, GNAI2B (HUMAN), GNB1 (HUMAN), GNG2 (HUMAN), ADORA1 (HUMAN)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ACM4_HUMAN] The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase. [GNAI2_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. May play a role in cell division.^[1] Isoform sGi2: Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool.^[2] [GBG2_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 (By similarity). [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.^[3]

Publication Abstract from PubMed

The class A adenosine A1 receptor (A1R) is a G-protein-coupled receptor that preferentially couples to inhibitory Gi/o heterotrimeric G proteins, has been implicated in numerous diseases, yet remains poorly targeted. Here we report the 3.6 A structure of the human A1R in complex with adenosine and heterotrimeric Gi2 protein determined by Volta phase plate cryo-electron microscopy. Compared to inactive A1R, there is contraction at the extracellular surface in the orthosteric binding site mediated via movement of transmembrane domains 1 and 2. At the intracellular surface, the G protein engages the A1R primarily via amino acids in the C terminus of the Galphai alpha5-helix, concomitant with a 10.5 A outward movement of the A1R transmembrane domain 6. Comparison with the agonist-bound beta2 adrenergic receptor-Gs-protein complex reveals distinct orientations for each G-protein subtype upon engagement with its receptor. This active A1R structure provides molecular insights into receptor and G-protein selectivity.

Structure of the adenosine-bound human adenosine A1 receptor-Gi complex.,Draper-Joyce CJ, Khoshouei M, Thal DM, Liang YL, Nguyen ATN, Furness SGB, Venugopal H, Baltos JA, Plitzko JM, Danev R, Baumeister W, May LT, Wootten D, Sexton PM, Glukhova A, Christopoulos A Nature. 2018 Jun;558(7711):559-563. doi: 10.1038/s41586-018-0236-6. Epub 2018 Jun, 20. PMID:29925945^[4]

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

References

↑ Cho H, Kehrl JH. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007 Jul 16;178(2):245-55. PMID:17635935 doi:10.1083/jcb.200604114
↑ Lopez-Aranda MF, Acevedo MJ, Gutierrez A, Koulen P, Khan ZU. Role of a Galphai2 protein splice variant in the formation of an intracellular dopamine D2 receptor pool. J Cell Sci. 2007 Jul 1;120(Pt 13):2171-8. Epub 2007 Jun 5. PMID:17550964 doi:http://dx.doi.org/jcs.005611
↑ Johnston CA, Kimple AJ, Giguere PM, Siderovski DP. Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2. Structure. 2008 Jul;16(7):1086-94. PMID:18611381 doi:http://dx.doi.org/10.1016/j.str.2008.04.010
↑ Draper-Joyce CJ, Khoshouei M, Thal DM, Liang YL, Nguyen ATN, Furness SGB, Venugopal H, Baltos JA, Plitzko JM, Danev R, Baumeister W, May LT, Wootten D, Sexton PM, Glukhova A, Christopoulos A. Structure of the adenosine-bound human adenosine A1 receptor-Gi complex. Nature. 2018 Jun;558(7711):559-563. doi: 10.1038/s41586-018-0236-6. Epub 2018 Jun, 20. PMID:29925945 doi:http://dx.doi.org/10.1038/s41586-018-0236-6

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/6d9h"

@@ Line 1: / Line 1: @@
 ==Cryo-EM structure of the human adenosine A1 receptor-Gi2-protein complex bound to its endogenous agonist==
-<StructureSection load='6d9h' size='340' side='right' caption='[[6d9h]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
+<SX load='6d9h' size='340' side='right' viewer='molstar' caption='[[6d9h]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6d9h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D9H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D9H FirstGlance]. <br>
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6d9h" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Transducin 3D structures|Transducin 3D structures]]
 == References ==
 <references/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Baltos, J]]
 [[Category: Baumeister, W]]

6d9h

From Proteopedia

Revision as of 20:52, 6 March 2020

Cryo-EM structure of the human adenosine A1 receptor-Gi2-protein complex bound to its endogenous agonist

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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