Architecture of the human NALCN channelosome.

ABSTRACT: NALCN regulates the resting membrane potential by mediating the Na⁺ leak current in neurons, and it functions as a channelosome in complex with FAM155A, UNC79, and UNC80. Dysfunction of the NALCN channelosome causes a broad range of neurological and developmental diseases called NALCN channelopathies in humans. How the auxiliary subunits, especially the two large components UNC79 and UNC80, assemble with NALCN and regulate its function remains unclear. Here we report an overall architecture of the human NALCN channelosome. UNC79 and UNC80 each adopt an S-shape super-helical structure consisting of HEAT and armadillo repeats, forming a super-coiled heterodimeric assembly in the cytoplasmic side, which may provide a scaffold for the binding of other potential modulators of the cha

SUBMITTER: Zhou L 

PROVIDER: S-EPMC8986805 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature