9jv1

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of transporter2a1_PGE2

Structural highlights

9jv1 is a 1 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 3.1Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SO2A1_HUMAN Defects in SLCO2A1 are the cause of hypertrophic osteoarthropathy, primary, autosomal recessive, type 2 (PHOAR2) [MIM:614441. PHOAR2 is a disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease.^[1] ^[2] ^[3] ^[4]

Function

SO2A1_HUMAN May mediate the release of newly synthesized prostaglandins from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. Transports PGD2, as well as PGE1, PGE2 and PGF2A.

Publication Abstract from PubMed

SLCO2A1 is a member of the organic anion transporting polypeptide (OATP) family, which preferentially transports prostaglandins (PGs) into cells and plays a vital role in regulating PGs inactivation and distribution. Dysregulation or genetic mutation of SLCO2A1 is associated with primary hypertrophic osteoarthropathy (PHO) and chronic enteropathy associated with the SLCO2A1 gene (CEAS). Although the biophysical and biochemical properties of SLCO2A1 have been characterized, the precise mechanism by which SLCO2A1 recognizes and transports PGs remains unclear. Here, we present the cryo-electron microscopy structures of human SLCO2A1 in apo and PGE(2)-bound forms, revealing the detailed structural features and structural basis for PGs transport. Fatty acid-like PGE(2) binds in the central cavity, engaging in specific interactions with W565 and two serine residues, which are not conserved in other OATPs. Combined with functional assays and structural comparisons, this study offers mechanistic insights into PGE(2) recognition, substrate selectivity, conformational changes, and pathology of SLCO2A1.

Structure and transport mechanism of the human prostaglandin transporter SLCO2A1.,Xia Z, Lu G, Wu D, Zhao J, Zhang B, Xu H, Du Y, Jiang D Nat Commun. 2025 Aug 30;16(1):8124. doi: 10.1038/s41467-025-63615-8. PMID:40885756^[5]

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

References

↑ Seifert W, Kuhnisch J, Tuysuz B, Specker C, Brouwers A, Horn D. Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated digital clubbing. Hum Mutat. 2012 Apr;33(4):660-4. doi: 10.1002/humu.22042. Epub 2012 Feb 24. PMID:22331663 doi:10.1002/humu.22042
↑ Zhang Z, Xia W, He J, Zhang Z, Ke Y, Yue H, Wang C, Zhang H, Gu J, Hu W, Fu W, Hu Y, Li M, Liu Y. Exome sequencing identifies SLCO2A1 mutations as a cause of primary hypertrophic osteoarthropathy. Am J Hum Genet. 2012 Jan 13;90(1):125-32. doi: 10.1016/j.ajhg.2011.11.019. Epub, 2011 Dec 22. PMID:22197487 doi:10.1016/j.ajhg.2011.11.019
↑ Diggle CP, Parry DA, Logan CV, Laissue P, Rivera C, Restrepo CM, Fonseca DJ, Morgan JE, Allanore Y, Fontenay M, Wipff J, Varret M, Gibault L, Dalantaeva N, Korbonits M, Zhou B, Yuan G, Harifi G, Cefle K, Palanduz S, Akoglu H, Zwijnenburg PJ, Lichtenbelt KD, Aubry-Rozier B, Superti-Furga A, Dallapiccola B, Accadia M, Brancati F, Sheridan EG, Taylor GR, Carr IM, Johnson CA, Markham AF, Bonthron DT. Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis. Hum Mutat. 2012 Aug;33(8):1175-81. doi: 10.1002/humu.22111. Epub 2012 May 29. PMID:22553128 doi:10.1002/humu.22111
↑ Busch J, Frank V, Bachmann N, Otsuka A, Oji V, Metze D, Shah K, Danda S, Watzer B, Traupe H, Bolz HJ, Kabashima K, Bergmann C. Mutations in the prostaglandin transporter SLCO2A1 cause primary hypertrophic osteoarthropathy with digital clubbing. J Invest Dermatol. 2012 Oct;132(10):2473-6. doi: 10.1038/jid.2012.146. Epub 2012 , Jun 14. PMID:22696055 doi:10.1038/jid.2012.146
↑ Xia Z, Lu G, Wu D, Zhao J, Zhang B, Xu H, Du Y, Jiang D. Structure and transport mechanism of the human prostaglandin transporter SLCO2A1. Nat Commun. 2025 Aug 30;16(1):8124. PMID:40885756 doi:10.1038/s41467-025-63615-8

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9jv1"

Categories: Homo sapiens | Large Structures | Jiang DH | Xia ZY

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9jv1 is ON HOLD  until Paper Publication
+==Cryo-EM structure of transporter2a1_PGE2==
+<StructureSection load='9jv1' size='340' side='right'caption='[[9jv1]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9jv1]] is a 1 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=9JV1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9JV1 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]] 3.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P2E:(Z)-7-[(1R,2R,3R)-3-HYDROXY-2-[(E,3S)-3-HYDROXYOCT-1-ENYL]-5-OXO-CYCLOPENTYL]HEPT-5-ENOIC+ACID'>P2E</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=9jv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9jv1 OCA], [https://pdbe.org/9jv1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9jv1 RCSB], [https://www.ebi.ac.uk/pdbsum/9jv1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9jv1 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/SO2A1_HUMAN SO2A1_HUMAN] Defects in SLCO2A1 are the cause of hypertrophic osteoarthropathy, primary, autosomal recessive, type 2 (PHOAR2) [MIM:[https://omim.org/entry/614441 614441]. PHOAR2 is a disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease.<ref>PMID:22331663</ref> <ref>PMID:22197487</ref> <ref>PMID:22553128</ref> <ref>PMID:22696055</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/SO2A1_HUMAN SO2A1_HUMAN] May mediate the release of newly synthesized prostaglandins from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. Transports PGD2, as well as PGE1, PGE2 and PGF2A.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+SLCO2A1 is a member of the organic anion transporting polypeptide (OATP) family, which preferentially transports prostaglandins (PGs) into cells and plays a vital role in regulating PGs inactivation and distribution. Dysregulation or genetic mutation of SLCO2A1 is associated with primary hypertrophic osteoarthropathy (PHO) and chronic enteropathy associated with the SLCO2A1 gene (CEAS). Although the biophysical and biochemical properties of SLCO2A1 have been characterized, the precise mechanism by which SLCO2A1 recognizes and transports PGs remains unclear. Here, we present the cryo-electron microscopy structures of human SLCO2A1 in apo and PGE(2)-bound forms, revealing the detailed structural features and structural basis for PGs transport. Fatty acid-like PGE(2) binds in the central cavity, engaging in specific interactions with W565 and two serine residues, which are not conserved in other OATPs. Combined with functional assays and structural comparisons, this study offers mechanistic insights into PGE(2) recognition, substrate selectivity, conformational changes, and pathology of SLCO2A1.
-Authors:
+Structure and transport mechanism of the human prostaglandin transporter SLCO2A1.,Xia Z, Lu G, Wu D, Zhao J, Zhang B, Xu H, Du Y, Jiang D Nat Commun. 2025 Aug 30;16(1):8124. doi: 10.1038/s41467-025-63615-8. PMID:40885756<ref>PMID:40885756</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 9jv1" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Jiang DH]]
+[[Category: Xia ZY]]

9jv1

From Proteopedia

Current revision

Cryo-EM structure of transporter2a1_PGE2

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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