PT - JOURNAL ARTICLE AU - Cheang, Qing Wei AU - Xin, Lingyi AU - Chea, Rachel Yuen Fong AU - Liang, Zhao-Xun TI - Emerging paradigms for PilZ domain-mediated C-di-GMP signaling AID - 10.1042/BST20180543 DP - 2019 Feb 01 TA - Biochemical Society Transactions PG - BST20180543 4099 - http://www.biochemsoctrans.org/content/early/2019/01/31/BST20180543.short 4100 - http://www.biochemsoctrans.org/content/early/2019/01/31/BST20180543.full AB - PilZ domain-containing proteins constitute a large family of bacterial signaling proteins. As a widely distributed protein domain for the binding of the second messenger c-di-GMP, the canonical PilZ domain contains a set of motifs that define the binding site for c-di-GMP and an allosteric switch for propagating local conformational changes. Here, we summarize some new insights gathered from recent studies on the commonly occurring single-domain PilZ proteins, YcgR-like proteins and PilZ domain-containing cellulose synthases. The studies collectively illuminate how PilZ domains function as cis- or trans-regulatory domains that enable c-di-GMP to control the activity of its cellular targets. Overall, the review highlights the diverse protein structure, biological function and regulatory mechanism of PilZ domain-containing proteins, as well as the challenge of deciphering the function and mechanism of orphan PilZ proteins.EPS, exopolysaccharides; GT, glycosyltransferase; MCP, methyl-accepting chemotaxis protein; PNAG, poly-β-1,6-N-acetylglucosamine; SAM, S-Adenosyl-Methionine