The non-structural protein NS5A is an active hepatitis C virus (HCV) replicase component, a pivotal regulator of replication, and a modulator of several cellular processes which range from innate immunity to dysregulated cell growth. NS5A is organized into three domains, labelled I, II and III. Domain I contains a zinc-binding motif and an amphipathic N-terminal helix which promotes membrane association. Mutations disrupting either the membrane anchor or zinc binding are lethal for RNA replication PMID:19244328,PMID:24639329.

Structural domains comprising this superfamily share the structure of domain 1B of the hepatitis C virus NS5A protein. One remarkable feature of this domain is the presence of a disulfide bond near its C-terminus. It has been shown that this domain not required for the RNA replicase functions of NS5A. However, the presence of the cited sulphide bond which tethering the C-terminus of domain I suggests that it is likely responsible of the structural arrangement of domains II and III, thus playing a regulatory role in NS5A function by serving as a conformation switch to modulate functions of NS5A in and out of the replicase PMID:15902263.