Structural insights into calcium-dependent CIB2-TMC1 interaction in hair cell mechanotransduction.

ABSTRACT: Calcium- and integrin-binding protein 2 (CIB2) plays a crucial role in mechanoelectrical transduction (MET) in cochlear hair cells, particularly in modulating the function and localization of the core components of MET channels TMC1/2. CIB2, along with its homolog CIB3, interacts with TMC1/2 through two distinct sites. Here, our study unveils CIB2/3's role as a calcium sensor in its interaction with TMC1. Utilizing X-ray crystallography, we elucidate the high-resolution structure of the mammalian CIB2-TMC1 complex. Structural analyses reveal that cation-bound CIB2 forms a negatively charged surface that aligns with a positively charged surface on the TMC1 N-terminus. Moreover, our data suggest that Ca²⁺ modulates CIB2's interaction with both the N-terminal domain and the loop 1 region of T

SUBMITTER: Li Y 

PROVIDER: S-EPMC11861898 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature