Identification of the Activator Binding Residues in the Second Cysteine-Rich Regulatory Domain of Protein Kinase C Theta
PKCθ is predominantly expressed in T-cells and critically involved in immunity. Design of PKCθ selective molecules to manage autoimmune disorders by targeting its activator binding C1 domain requires the knowledge of its structure and the activator binding residues. The C1 domain consists of twin C1 domains, C1A and C1B, of which C1B plays the critical role in the membrane translocation and activation of PKCq. Here, we determined the crystal structure of the PKCθC1B to 1.63Å resolution, which showed that the Trp-253 at the rim of the activator binding pocket was oriented towards the membrane whe...
Source: BJ Signal - January 4, 2013 Category: Biochemistry Authors: G M Rahman, S Shanker, N E Lewin, N Kedei, C S Hill, B Prasad, P Blumberg, J Das Tags: BJ Signal Source Type: research
Subtype-selective regulation of IP3 receptors by thimerosal via cysteine residues within the IP3-binding core and suppressor domain.
Inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors are the most widely expressed intracellular Ca2+ channels and both are regulated by sulphydryl reagents. In DT40 cells stably expressing single subtypes of mammalian IP3R, low concentrations of thimerosal, which oxidises thiols to form a thiomercurylethyl complex, increased the sensitivity of IP3-evoked Ca2+ release via IP3R1 and IP3R2, but inhibited IP3R3. Activation of IP3R is initiated by IP3 binding to the IP3-binding core (IBC, residues 224-604) and proceeds via re-arrangement of an interface between the IBC and suppressor domain (SD, ...
Source: BJ Signal - January 2, 2013 Category: Biochemistry Authors: S A. Khan, A M Rossi, A M Riley, B V.L. Potter, C W. Taylor Tags: BJ Signal Source Type: research
