Figure 7. A model for distinct routes across the ER translocon.

Large proteins (on the left) are co-translationally translocated across the ER in a process dependent upon the SRP receptor complex (SR). Short proteins (on the right) utilize a post-translational route(s) that require the Sec62/63 complex. Both routes are independent of the properties of the signal sequence (1). However, the signal sequence appears to affect how the precursor engages with the translocon both co- and post-translationally (2), as reflected in differing sensitivity to CPD A. The signal sequence may also determine whether BiP is required for the efficient translocation of short secretory proteins. Dashed arrows suggest how a specific mode of engagement of the signal sequence with the translocon might enable BiP to support translocation.