15.6
La translocation co-traductionnelle des protéines
La translocation des protéines à travers les membranes est un processus ancien qu’on retrouve même chez les bactéries et les archéobactéries. En fait,…
La plupart des protéines pénètrent dans la lumière du RE alors qu’elles sont encore en synthèse – un processus appelé translocation cotraductionnelle.
Tout d’abord, le complexe récepteur SRP-SRP portant le complexe de la chaîne naissante du ribosome le décharge sur le canal Sec61.
Une fois que le ribosome s’aligne avec le canal, la séquence de signal à la borne N de la chaîne polypeptidique s’accroche à un site de reconnaissance de séquence de signaux.
Au fur et à mesure que la traduction se poursuit, la chaîne polypeptidique forme une boucle qui ouvre le bouchon du canal pour l’entrée dans la lumière du RE.
Alors que le polypeptide descend dans la lumière, la séquence de signaux sort par la porte latérale du canal Sec61 pour entrer dans le complexe de peptidase signal adjacent, où elle est clivée.
Le bouchon du canal reste ouvert pendant que la protéine descend passivement dans la lumière du RE.
Après une translocation complète de la protéine dans la lumière, le bouchon du canal rebondit pour empêcher la protéine de retourner dans le cytosol.
À l’intérieur de la lumière du RE, des chaperons résidents du RE comme BiP lient immédiatement la protéine transloquée et aident au repliement des protéines.
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Q1: What is cotranslational protein translocation and how does it differ from other translocation methods?
Cotranslational protein translocation occurs while proteins are still being synthesized by ribosomes. The nascent polypeptide chain enters the ER lumen during translation, contrasting with post-translational translocation of proteins to the RER, where proteins are fully synthesized before translocation. This simultaneous synthesis and translocation process is mediated by the SRP-SRP receptor complex and the Sec61 channel.
Q2: How does the Sec61 channel facilitate protein entry into the ER lumen?
The Sec61 channel contains a plug that blocks the channel opening. When the signal sequence of the nascent polypeptide latches onto a recognition site, it pushes the plug open, creating an entry pathway. As translation continues, the polypeptide descends passively through the channel into the ER lumen. After translocation completes, the channel plug bounces back to seal the channel and prevent protein return to the cytosol.
Q3: What role does the signal sequence play in cotranslational translocation?
The signal sequence at the N-terminal of the nascent polypeptide chain recognizes and latches onto a specific signal sequence recognition site on the Sec61 channel. This interaction triggers channel opening and initiates translocation. The signal sequence then exits through the lateral gate of the Sec61 channel to enter the signal peptidase complex, where it is cleaved off during translocation.
Q4: What are the key protein components that work with the Sec61 channel during cotranslational translocation?
The signal recognition particle (SRP) and SRP receptor (SR) deliver the ribosome-nascent chain complex to the Sec61 channel through GTP hydrolysis. Accessory proteins like the translocon-associated protein (TRAP) complex stabilize weak signal sequences, while the TRAM protein acts as a chaperone assisting in folding and membrane integration of translocating proteins.
Q5: How do ribosomes contribute to protein movement through the Sec61 channel?
Ribosomes act as primary translocation motors, pushing the nascent polypeptide chain toward the ER lumen during translation elongation. The ribosome aligns with the Sec61 channel, and as peptide bonds form, the growing polypeptide is propelled through the channel. This process requires no additional energy beyond the GTP hydrolysis used for normal peptide chain elongation.
Q6: What happens to proteins after they complete translocation into the ER lumen?
Once the polypeptide fully enters the ER lumen, the Sec61 channel plug closes to prevent protein return to the cytosol. Resident ER chaperones, particularly BiP, immediately bind the translocated protein and assist in proper protein folding. This quality control mechanism ensures proteins achieve their correct three-dimensional structure within the ER environment.
Q7: Why is the TRAP complex essential for proteins with low-hydrophobicity signal sequences?
The TRAP complex is a substrate-specific auxiliary component that stabilizes signal sequences with weak hydrophobic interactions. It directly interacts with the Sec61 channel and maintains the channel in an open conformation, compensating for the reduced binding strength between the signal sequence and the channel. This ensures secure anchoring and successful translocation of these challenging substrates.