6a70 | pdb_00006a70

Structure of the human PKD1/PKD2 complex

Loading... Status: waiting for Mol* initialization Structural highlights 6a70 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: PKD2, TRPP2 (HUMAN), PKD1 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [PKD2_HUMAN] Defects in PKD2 are the cause of polycystic kidney disease 2 (PKD2) [MIM:613095]. PKD2 is a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occurs in the liver and other organs. It represents approximately 15% of the cases of autosomal dominant polycystic kidney disease. PKD2 is clinically milder than PKD1 but it has a deleterious impact on overall life expectancy. [PKD1_HUMAN] Defects in PKD1 are the cause of polycystic kidney disease 1 (PKD1) [MIM:173900]. PKD1 is characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occurs in the liver and other organs. Its prevalence is estimated at about 1/1000. Function [PKD2_HUMAN] Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). PKD1 and PKD2 may function through a common signaling pathway that is necessary for normal tubulogenesis (By similarity). Acts as a regulator of cilium length, together with PKD1 (By similarity). The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (By similarity). Functions as a calcium permeable cation channel. [PKD1_HUMAN] Involved in renal tubulogenesis. Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). Acts as a regulator of cilium length, together with PKD2 (By similarity). The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (By similarity). May be an ion-channel regulator. Involved in adhesive protein-protein and protein-carbohydrate interactions. Publication Abstract from PubMed Mutations in two genes, pkd1 and pkd2, account for most cases of autosomal dominant polycystic kidney disease (ADPKD), one of the most common monogenetic disorders. Here we report the 3.6 A cryo-EM structure of truncated human PKD1/PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet non-canonical, TRP channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular S6a resembling pore helix 1 in a typical TRP channel. Three positively charged cavity-facing residues on S6b may block cation permeation. In addition to VGIC, a 5-TM domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1/PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins. Structure of the human PKD1/PKD2 complex.,Su Q, Hu F, Ge X, Lei J, Yu S, Wang T, Zhou Q, Mei C, Shi Y Science. 2018 Aug 9. pii: science.aat9819. doi: 10.1126/science.aat9819. PMID:30093605 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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