Structural basis for Ca²⁺ activation of the heteromeric PKD1L3/PKD2L1 channel.

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 Ca²⁺ and acid-induced channel activities. Cryo-EM structures of this core heterocomplex with or without supplemented Ca²⁺ 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. Ca²⁺-entrance to the SF vest

SUBMITTER: Su Q 

PROVIDER: S-EPMC8357825 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature