Secondary-structure switch regulates the substrate binding of a YopJ family acetyltransferase
Yao Xia, Rongfeng Zou, Maxime Escouboué, Liang Zhong, Chengjun Zhu, Cécile Pouzet, Xueqiang Wu, Yongjin Wang, Guohua Lv, Haibo Zhou, Pinghua Sun, Ke Ding, Laurent Deslandes, Shuguang Yuan, Zhimin Zhang
Abstract
The Yersinia outer protein J (YopJ) family effectors are widely deployed through the type III secretion system by both plant and animal pathogens. As non-canonical acetyltransferases, the enzymatic activities of YopJ family effectors are allosterically activated by the eukaryote-specific ligand inositol hexaphosphate (InsP6). However, the underpinning molecular mechanism remains undefined. Here we present the crystal structure of apo-PopP2, a YopJ family member secreted by the plant pathogen Ralstonia solanacearum. Structural comparison of apo-PopP2 with the InsP6-bound PopP2 reveals a substantial conformational readjustment centered in the substrate-binding site. Combining biochemical and computational analyses, we further identify a mechanism by which the association of InsP6 with PopP2 induces an α-helix-to-β-strand transition in the catalytic core, resulting in stabilization of the substrate recognition helix in the target protein binding site. Together, our study uncovers the molecular basis governing InsP6-mediated allosteric regulation of YopJ family acetyltransferases and further expands the paradigm of fold-switching proteins.