7x1j | pdb_00007x1j

Cryo-EM structure of human BTR1 in the outward-facing state in the presence of NH4Cl.

spinqualitylabelsall models 7x1j, resolution 2.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7x1j is a 2 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 2.84Å Ligands: PT5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease S4A11_HUMAN Corneal dystrophy-perceptive deafness syndrome;Fuchs endothelial corneal dystrophy;Congenital hereditary endothelial dystrophy type II. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Function S4A11_HUMAN Multifunctional transporter with an impact in cell morphology and differentiation. In the presence of borate B(OH)4(-), acts as a voltage-dependent electrogenic Na(+)-coupled B(OH)4(-) cotransporter controlling boron homeostasis (PubMed:15525507). At early stages of stem cell differentiation, participates in synergy with ITGA5-ITGB1 and ITGAV-ITGB3 integrins and BMPR1A to promote cell adhesion and contractility that drives differentiation toward osteogenic commitment while inhibiting adipogenesis (By similarity). In the absence of B(OH)4(-), acts as a Na(+)-coupled OH(-) or H(+) permeable channel with implications in cellular redox balance (PubMed:15525507, PubMed:28642546). Regulates the oxidative stress response in corneal endothelium by enhancing antioxidant defenses and protecting cells from reactive oxygen species (PubMed:28642546). In response to hypo-osmotic challenge, also acts as water permeable channel at the basolateral cell membrane of corneal endothelial cells and facilitates transendothelial fluid reabsorption in the aqueous humor (PubMed:31273259, PubMed:25007886, PubMed:23813972). In the presence of ammonia, acts as an electrogenic NH3/H(+) cotransporter and may play a role in ammonia transport and reabsorption in renal Henle's loop epithelium (PubMed:27581649).[UniProtKB:A2AJN7] Publication Abstract from PubMed BTR1 (SLC4A11) is a NH(3) stimulated H(+) (OH(-)) transporter belonging to the SLC4 family. Dysfunction of BTR1 leads to diseases such as congenital hereditary endothelial dystrophy (CHED) and Fuchs endothelial corneal dystrophy (FECD). However, the mechanistic basis of BTR1 activation by alkaline pH, transport activity regulation and pathogenic mutations remains elusive. Here, we present cryo-EM structures of human BTR1 in the outward-facing state in complex with its activating ligands PIP(2) and the inward-facing state with the pathogenic R125H mutation. We reveal that PIP(2) binds at the interface between the transmembrane domain and the N-terminal cytosolic domain of BTR1. Disruption of either the PIP(2) binding site or protonation of PIP(2) phosphate groups by acidic pH can transform BTR1 into an inward-facing conformation. Our results provide insights into the mechanisms of how the transport activity and conformation changes of BTR1 are regulated by PIP(2) binding and interaction of TMD and NTD. Structural insights into the conformational changes of BTR1/SLC4A11 in complex with PIP(2).,Lu Y, Zuo P, Chen H, Shan H, Wang W, Dai Z, Xu H, Chen Y, Liang L, Ding D, Jin Y, Yin Y Nat Commun. 2023 Oct 3;14(1):6157. doi: 10.1038/s41467-023-41924-0. PMID:37788993 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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