This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
5k47
From Proteopedia
CryoEM structure of the human Polycystin-2/PKD2 TRP channel
Structural highlights
DiseasePKD2_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.[1] [2] [3] [4] [5] [6] [7] [8] [9] FunctionPKD2_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. Publication Abstract from PubMedMutations in either polycystin-1 (PC1 or PKD1) or polycystin-2 (PC2, PKD2 or TRPP1) cause autosomal-dominant polycystic kidney disease (ADPKD) through unknown mechanisms. Here we present the structure of human PC2 in a closed conformation, solved by electron cryomicroscopy at 4.2-A resolution. The structure reveals a novel polycystin-specific 'tetragonal opening for polycystins' (TOP) domain tightly bound to the top of a classic transient receptor potential (TRP) channel structure. The TOP domain is formed from two extensions to the voltage-sensor-like domain (VSLD); it covers the channel's endoplasmic reticulum lumen or extracellular surface and encloses an upper vestibule, above the pore filter, without blocking the ion-conduction pathway. The TOP-domain fold is conserved among the polycystins, including the homologous channel-like region of PC1, and is the site of a cluster of ADPKD-associated missense variants. Extensive contacts among the TOP-domain subunits, the pore and the VSLD provide ample scope for regulation through physical and chemical stimuli. Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2).,Grieben M, Pike AC, Shintre CA, Venturi E, El-Ajouz S, Tessitore A, Shrestha L, Mukhopadhyay S, Mahajan P, Chalk R, Burgess-Brown NA, Sitsapesan R, Huiskonen JT, Carpenter EP Nat Struct Mol Biol. 2016 Dec 19. doi: 10.1038/nsmb.3343. PMID:27991905[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
Categories: Homo sapiens | Large Structures | Arrowsmith CH | Bountra C | Burgess-Brown NA | Carpenter EP | Chalk R | Edwards AM | Grieben M | Huiskonen JT | Mahajan P | Mukhopadhyay S | Pike ACW | Shintre CA | Shrestha L | Tessitore A
