PilZ domain-containing protein (PilZ)

PilZ domain-containing proteins are a large family of bacterial signaling proteins that serve as the primary cytoplasmic receptors for the second messenger cyclic diguanylate (c-di-GMP)[1][3]. The canonical PilZ domain is characterized by a conserved structure of six β-strands followed by a C-terminal α-helix, forming a binding site for c-di-GMP through specific sequence motifs (RxxxR and D/NxSxxG)[2][3]. Binding of c-di-GMP induces conformational changes that enable the PilZ domain to regulate the activity of its target proteins, acting either as a cis- or trans-regulatory domain[1]. These proteins are widely distributed in bacteria and are involved in diverse processes such as motility (e.g., acting as a “flagellar brake”), biofilm formation, cellulose synthesis, and type IV pilus biogenesis[1][3][6]. Elevated intracellular c-di-GMP, sensed by PilZ domains, generally promotes a switch from a motile, planktonic lifestyle to a sessile, biofilm-forming state[3]. There are also atypical and divergent PilZ-related domains with varied structures and functions, some of which have lost c-di-GMP binding capacity but retain roles in pilus regulation or other cellular processes[2]. While the PilZ domain itself is not currently a direct therapeutic target, its central role in bacterial virulence and biofilm formation makes it a potential indirect target for anti-infective strategies[1][3][6]. However, there are no known drugs that directly interact with the PilZ domain, and its primary significance is in bacterial physiology and pathogenesis[1][3].

Other names

YcgRYcgR-like proteinPilZ domain proteinc-di-GMP receptorcellulose synthase associated PilZ domainPilZ domain effector