7D7F

Structure of PKD1L3-CTD/PKD2L1 in calcium-bound state

Summary for 7D7F

• Entry DOI: 10.2210/pdb7d7f/pdb
• EMDB information: 30607
• Descriptor: Polycystic kidney disease 2-like 1 protein, Polycystic kidney disease protein 1-like 3, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: heterotetrameric trp channel, calcium, primary cilia, pkd, transport protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 4
• Total formula weight: 272658.59

Authors

Su, Q.,Shi, Y.G. (deposition date: 2020-10-03, release date: 2021-09-01, Last modification date: 2024-11-20)

Primary citation

Su, Q.,Chen, M.,Wang, Y.,Li, B.,Jing, D.,Zhan, X.,Yu, Y.,Shi, Y.
Structural basis for Ca 2+ activation of the heteromeric PKD1L3/PKD2L1 channel.
Nat Commun, 12:4871-4871, 2021

PubMed Abstract: The heteromeric complex between PKD1L3, a member of the polycystic kidney disease (PKD) protein family, and PKD2L1, also known as TRPP2 or TRPP3, has been a prototype for mechanistic characterization of heterotetrametric TRP-like channels. Here we show that a truncated PKD1L3/PKD2L1 complex with the C-terminal TRP-fold fragment of PKD1L3 retains both Ca and acid-induced channel activities. Cryo-EM structures of this core heterocomplex with or without supplemented Ca were determined at resolutions of 3.1 Å and 3.4 Å, respectively. The heterotetramer, with a pseudo-symmetric TRP architecture of 1:3 stoichiometry, has an asymmetric selectivity filter (SF) guarded by Lys2069 from PKD1L3 and Asp523 from the three PKD2L1 subunits. Ca-entrance to the SF vestibule is accompanied by a swing motion of Lys2069 on PKD1L3. The S6 of PKD1L3 is pushed inward by the S4-S5 linker of the nearby PKD2L1 (PKD2L1-III), resulting in an elongated intracellular gate which seals the pore domain. Comparison of the apo and Ca-loaded complexes unveils an unprecedented Ca binding site in the extracellular cleft of the voltage-sensing domain (VSD) of PKD2L1-III, but not the other three VSDs. Structure-guided mutagenic studies support this unconventional site to be responsible for Ca-induced channel activation through an allosteric mechanism.

PubMed: 34381056
DOI: 10.1038/s41467-021-25216-z

Experimental method

ELECTRON MICROSCOPY (3.1 Å)