8ghj

Crystal structure of human AQP2 T125M mutant

spinqualitylabelsall models 8ghj, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ghj 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: X-ray diffraction, Resolution 3.9Å Ligands: CD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease AQP2_HUMAN Nephrogenic diabetes insipidus. The disease is caused by mutations affecting the gene represented in this entry. Function AQP2_HUMAN Forms a water-specific channel that provides the plasma membranes of renal collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. Publication Abstract from PubMed Aquaporins are water channels found in the cell membrane, where they allow the passage of water molecules in and out of the cells. In the kidney collecting duct, arginine vasopressin-dependent trafficking of aquaporin-2 (AQP2) fine-tunes reabsorption of water from pre-urine, allowing precise regulation of the final urine volume. Point mutations in the gene for AQP2 may disturb this process and lead to nephrogenic diabetes insipidus (NDI), whereby patients void large volumes of highly hypo-osmotic urine. In recessive NDI, mutants of AQP2 are retained in the endoplasmic reticulum due to misfolding. Here we describe the structural and functional characterization of three AQP2 mutations associated with recessive NDI: T125M and T126M, situated close to a glycosylation site and A147T in the transmembrane region. Using a proteoliposome assay, we show that all three mutants permit the transport of water. The crystal structures of T125M and T126M together with biophysical characterization of all three mutants support that they retain the native structure, but that there is a significant destabilization of A147T. Our work provides unique molecular insights into the mechanisms behind recessive NDI as well as deepens our understanding of how misfolded proteins are recognized by the ER quality control system. Structural and functional analysis of aquaporin-2 mutants involved in nephrogenic diabetes insipidus.,Hagstromer CJ, Hyld Steffen J, Kreida S, Al-Jubair T, Frick A, Gourdon P, Tornroth-Horsefield S Sci Rep. 2023 Sep 6;13(1):14674. doi: 10.1038/s41598-023-41616-1. PMID:37674034 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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