Distinctive phosphoinositide- and Ca²⁺-binding properties of normal and cognitive performance-linked variant forms of KIBRA C2 domain.

ABSTRACT: Kidney- and brain-expressed protein (KIBRA), a multifunctional scaffold protein with around 20 known binding partners, is involved in memory and cognition, organ size control via the Hippo pathway, cell polarity, and membrane trafficking. KIBRA includes tandem N-terminal WW domains, a C2 domain, and motifs for binding atypical PKC and PDZ domains. A naturally occurring human KIBRA variant involving residue changes at positions 734 (Met-to-Ile) and 735 (Ser-to-Ala) within the C2 domain affects cognitive performance. We have elucidated 3D structures and calcium- and phosphoinositide-binding properties of human KIBRA C2 domain. Both WT and variant C2 adopt a canonical type I topology C2 domain fold. Neither Ca²⁺ nor any other metal ion was bound to WT or variant KIBRA C2 in crystal

SUBMITTER: Posner MG 

PROVIDER: S-EPMC6005455 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature