The essential steps in cotranslational translocation. (A) SRP-dependent targeting of a signal- or TMD-containing nascent chain to the Sec61 translocon. (B) Modes of interaction between signals and TMDs with the Sec61 translocon. (C) The diversity of signal sequences: the overall length and net charge of the n domain (green) are listed for a set of typical signals. The hydrophobic core of each signal sequence is indicated in red underlined text.