Domain interactions in E-coli SRP: Stabilization of M domain by RNA is required for effective signal sequence modulation of NG domain

The E. coli protein, Ffh, binds to 4.5S RNA through its M domain to form the signal recognition particle (SRP). The other domain of Ffh (NG) is a GTPase, which binds and is coordinately regulated by its receptor, FtsY. We find that the helical M domain is inherently flexible. Binding of 4.5S RNA to Ffh stabilizes the M domain yet has little apparent effect on the binding of signal peptides. However, in the absence of the RNA, signal peptide binding results in a global destabilization of Ffh, which is prevented by binding of 4.5S RNA. Signal peptide binding to isolated NG domain also causes a pronounced destabilization, implicating the No domain in direct recognition of signal peptide.