GTP-DEPENDENT CONFORMATIONAL-CHANGES ASSOCIATED WITH THE FUNCTIONAL SWITCH BETWEEN G-ALPHA AND CROSS-LINKING ACTIVITIES IN BRAIN-DERIVED TISSUE TRANSGLUTAMINASE

GTP and Ca2+, two well-known modulators of intracellular signaling pat hways, control a structural/functional switch between two vital and mu tually exclusive activities, cross-linking and G(alpha) activity, in t he same enzyme. The enzyme, a brain-derived tissue-type transglutamina se (TGase), was recently cloned by us in two forms, one of which (s-TG N) lacks a C-terminal region that is present in the other (1-TGN). Imm unoreaction with antibodies directed against a peptide present in the C-terminus of 1-TGN but missing in s-TGN suggested that this site, whi ch is located in the C-terminal fourth domain, undergoes conformationa l changes as a result of interaction between 1-TGN and GTP. Site-direc ted mutagenesis suggested that the third domain is involved in mediati ng the inhibition of the cross-linking activity. These results were su pported by molecular modeling, which further suggested that domains II I and IV both participate in conformational changes leading to the fun ctional switch between the Ca2+-dependent cross-linking activity and t he G(alpha) activity. (C) 1998 Academic Press.