PMID: 27991905

 

    Legend: Gene, Sites

Title : Structure of the polycystic kidney disease TRP channel Polycystin-2 ( PC2 )

Abstract :

1. Mutations in either polycystin-1 ( PC1 or PKD1 ) or polycystin-2 ( PC2 , PKD2 or TRPP1 ) cause autosomal-dominant polycystic kidney disease (ADPKD) through unknown mechanisms
2. Here we present the structure of human PC2 in a closed conformation, solved by electron cryomicroscopy at 4.2-Å resolution
3. 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
4. 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
5. 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
6. Extensive contacts among the TOP-domain subunits , the pore and the VSLD provide ample scope for regulation through physical and chemical stimuli

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

• 5. PC1, region
• 5. channel, region

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
PC2	5311	0,1,2
PKD2	5311	1
PKD1	5310	1
PC1	5310	1,5
polycystin-1	5310	1
TRPP1	5310	1
polycystin-2	5311	1
Polycystin-2	5311	0