9k1c

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of the DHA bound FFA1-Gi complex

Structural highlights

9k1c is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GNAI1_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. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.^[1] ^[2]

Publication Abstract from PubMed

Free fatty acid receptors (FFARs) play critical roles in metabolic regulation and are potential therapeutic targets for metabolic and inflammatory diseases. A comprehensive understanding of the activation mechanisms and endogenous ligand selectivity of FFARs is essential for drug discovery. Here, we report two cryoelectron microscopy structures of the human FFAR1 bound to the endogenous ligand docosahexaenoic acid (DHA) and G(i1) protein as well as FFAR2 in complex with butyrate and G(i1) at 3.2 A and 3.3 A resolution, respectively. These structures highlight that distinct locations and sizes of the orthosteric ligand binding pockets are crucial determinants of the endogenous ligand selectivity of this receptor subfamily. Additionally, computational analysis reveals a potential allosteric ligand binding pocket in FFAR2. Furthermore, we observe that the upward movement of helix V upon endogenous ligand binding is responsible for receptor activation. These insights will significantly aid in the development of drugs targeting this receptor family.

Structural insights into endogenous ligand selectivity and activation mechanisms of FFAR1 and FFAR2.,Ke Y, Huang Y, Yi C, Ma L, Chu X, Wu B, Zhao Q, Han S Cell Rep. 2024 Nov 30;43(12):115024. doi: 10.1016/j.celrep.2024.115024. PMID:39616615^[3]

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
↑ Johnston CA, Siderovski DP. Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2001-6. Epub 2007 Jan 30. PMID:17264214
↑ Ke Y, Huang Y, Yi C, Ma L, Chu X, Wu B, Zhao Q, Han S. Structural insights into endogenous ligand selectivity and activation mechanisms of FFAR1 and FFAR2. Cell Rep. 2024 Nov 30;43(12):115024. PMID:39616615 doi:10.1016/j.celrep.2024.115024

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9k1c"

Categories: Homo sapiens | Large Structures | Han S | Wu B | Zhao Q

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9k1c is ON HOLD
+==Cryo-EM structure of the DHA bound FFA1-Gi complex==
+<StructureSection load='9k1c' size='340' side='right'caption='[[9k1c]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9k1c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9K1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9K1C FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HXA:DOCOSA-4,7,10,13,16,19-HEXAENOIC+ACID'>HXA</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9k1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9k1c OCA], [https://pdbe.org/9k1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9k1c RCSB], [https://www.ebi.ac.uk/pdbsum/9k1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9k1c ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/GNAI1_HUMAN GNAI1_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. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> <ref>PMID:17264214</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Free fatty acid receptors (FFARs) play critical roles in metabolic regulation and are potential therapeutic targets for metabolic and inflammatory diseases. A comprehensive understanding of the activation mechanisms and endogenous ligand selectivity of FFARs is essential for drug discovery. Here, we report two cryoelectron microscopy structures of the human FFAR1 bound to the endogenous ligand docosahexaenoic acid (DHA) and G(i1) protein as well as FFAR2 in complex with butyrate and G(i1) at 3.2 A and 3.3 A resolution, respectively. These structures highlight that distinct locations and sizes of the orthosteric ligand binding pockets are crucial determinants of the endogenous ligand selectivity of this receptor subfamily. Additionally, computational analysis reveals a potential allosteric ligand binding pocket in FFAR2. Furthermore, we observe that the upward movement of helix V upon endogenous ligand binding is responsible for receptor activation. These insights will significantly aid in the development of drugs targeting this receptor family.
-Authors:
+Structural insights into endogenous ligand selectivity and activation mechanisms of FFAR1 and FFAR2.,Ke Y, Huang Y, Yi C, Ma L, Chu X, Wu B, Zhao Q, Han S Cell Rep. 2024 Nov 30;43(12):115024. doi: 10.1016/j.celrep.2024.115024. PMID:39616615<ref>PMID:39616615</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9k1c" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Han S]]
+[[Category: Wu B]]
+[[Category: Zhao Q]]

9k1c

From Proteopedia

Current revision

Cryo-EM structure of the DHA bound FFA1-Gi complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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