Fig. 6: Toxin-neutralization mechanism in the HipBST TA systems.
a Overlay of apo pHipTLp and structure of HipTLp–HipSLp in cartoon representation. Apo pHipTLp is colored gray and its P-loop is colored yellow, whereas HipTLp from the binary complex is colored cyan and its P-loop is colored purple. HipSLp is colored green. b Close-up view of the overlay showing that HipSLp binding induces conformational change of the P-loop. c Overlay of the pHipTLp–AMP–PNP and the structure of HipTLp–HipSLp in cartoon representation. pHipTLp from the pHipTLp–AMP–PNP is colored white. The HipTLp–HipSLp complex is color-coded as in panel a. d Close-up view of the overlapping between HipTLp residues and AMP–PNP. AMP–PNP is shown as dotted surface mode and overlapping HipTLp residues are shown as sticks. e Crystal structure of HipBSTO127 (PDB:7AB5) HipTO127, HipSO127 and HipBO127 were colored cyan, green and yellow orange, respectively. f Structural comparison between the HipTLp–HipSLp and HipBSTO127. The P-loops of HipTLp and HipTO127 are colored red and blue, respectively. g ITC thermogram and binding curve demonstrated that the HipTLp–HipSLp complex does not display detectable affinity for AMP–PNP. h Proposed model for toxin-neutralization mechanism in the HipBST TA systems. The toxin HipT is a Ser/Thr kinase in which the P-loop motif is vital for ATP binding and subsequent substrate phosphorylation. Binding of the antitoxin HipS causes conformational changes in the P-loop, which blocks ATP binding and ultimately inhibits the kinase activity of HipT.
