9juq
From Proteopedia
Cryo-EM structure of transporter2a1
Structural highlights
DiseaseSO2A1_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] FunctionSO2A1_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 PubMedSLCO2A1 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
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