Preferential Binding of Mg²⁺ Over Ca²⁺ to CIB2 Triggers an Allosteric Switch Impaired in Usher Syndrome Type 1J.

ABSTRACT: Calcium and integrin binding protein 2 (CIB2) shares with the other members of the CIB family the ability to bind Ca²⁺ and Mg²⁺ via two functional EF-hand motifs, namely EF3 and EF4. As a cation sensor, CIB2 is able to switch to a conformation likely associated with specific biological functions yet to be clarified. Recent findings demonstrate the involvement of CIB2 in hearing physiology and a single, conservative point mutation (p.E64D) has been related to Usher Syndrome type 1J (USH1J) and non-syndromic hearing loss. We present an exhaustive biochemical and biophysical characterization of human wild type (WT) and E64D CIB2. We found that CIB2 does not possibly work as a calcium sensor under physiological conditions, its affinity for Ca²⁺ (K_d

SUBMITTER: Vallone R 

PROVIDER: S-EPMC6107761 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature