SctU

SctU is a conserved component of bacterial type III secretion systems (T3SS), a needle-like machinery used by many Gram-negative pathogens to inject proteins into host cells. It is an inner-membrane protein that forms part of the T3SS export apparatus, linking the cytoplasmic complex to the membrane-embedded secretion channel. SctU is found across various bacteria, with well-known orthologs such as YscU in Yersinia and SpaS in Salmonella.

Structurally, SctU is associated with the inner membrane and is involved in the assembly of the secretion apparatus. A defining feature of SctU and its homologs is autoproteolytic processing at a conserved motif, commonly referred to as NPTH. This autoproteolysis cleaves SctU into two fragments, which typically remain associated and are required for proper function of the secretion system.

Functionally, SctU acts as a gatekeeper that regulates the order of substrate secretion by the T3SS. During initial assembly, early substrates that form the basal body and the needle are secreted. Once the needle complex is correctly assembled, the autoproteolytic processing of SctU enables the switch to secreting later substrates, including translocators and effector proteins. This regulatory role helps coordinate assembly with substrate delivery and prevents premature secretion.

Mutations that disrupt SctU processing or function often impair T3SS activity, leading to defects in substrate specificity and effector translocation. Given its central role, SctU is a key target for understanding T3SS regulation and for studying bacterial pathogenesis.