Which proteins are transported via this pathway?
integral membrane proteins (with trans-membrane domain)
secreted proteins
some housekeeping proteins
in totlal around 40% of the proteome
Which components are necessary for this transport pathway?
ribosome
signal sequence (SS) of the protein
signal recognition particle (SRP)
signal receptor (SR)
translocon (SecYEG, pore of the ER)
Describe the process of co-translational transport of proteins in the ER.
Signal sequence (SS): certain hydrophobic sequence at the N-terminus of the peptide chain that is being synthesized.
Some proteins have additional TMD (trans-membrane domain) to be inserted into the membrane.
The signal sequence is recognized by the signal recognition particle (SRP) and the translation is stalled.
The ribosome-mRNA-SRP complex is transported to a pore (translocon) of the ER, recognized by a signal receptor (SR)
Process of recognition and translocation:
a: Cargo recognition. SRP interacts with both sides of the ribosomal exit channel. Its fingerloop interacts with the signal sequence of the nascent protein.
b: Early complex. Upon GTP binding, SRP’s NG domains hetero-dimerize. Formerly unstructured domains become structured, the fingerloop wraps around the signal sequence more closely.
c: Closed complex. The NG-heterodimer domains detach from the ribosome. The unstructured A domain becomes available.
d: Activated complex. The unstructured A domain anchors the complex to the membrane. GTP hydrolysis is triggered, the fingerloop opens, and the signal sequence is handed over to translocon.
e: Translocation. The nascent peptide chain is detached from the ribosome. Translocation/Insertion into the membrane through translocon activity takes place.
Where does the energy of the process come from?
ribosomal translation (“pushing” of the protein)
folding inside the ER prevents “backsliding” of the protein, pulling force
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