The Sec pathway. (A) Posttranslational pathway: after complete synthesis at the ribosome, the unfolded preprotein is recognized by the molecular chaperone SecB (blue) and targeted to SecA (green). SecA guides the preprotein through the SecYEG pore (lime), employing the energy from ATP binding and hydrolysis. The signal peptide is cleaved by the signal peptidase (SPase [yellow]). SecDF (pink) pulls the preprotein across the membrane at the expense of the PMF. (B) Cotranslational pathway: once a hydrophobic transmembrane domain of a nascent membrane protein emerges from the ribosomes, signal recognition particle (SRP) (brown) binds to the ribosome nascent chain (RNC) and guides the complex to the SR receptor FtsY (dark brown) at the membrane. Upon the binding of GTP to the SRP:FtsY heterodimer, the RNC is released from SRP and transferred to the SecYEG channel, where chain elongation at the ribosome is directly coupled to membrane insertion of the nascent membrane protein.