Structural basis of SecA-mediated protein translocation

Area of Science:

• Molecular biology
• Structural biology
• Biochemistry

Background:

• Secretory proteins cross lipid membranes via protein-conducting channels like SecY (prokaryotes) and Sec61 (eukaryotes).
• SecA ATPase is crucial for posttranslational protein translocation across the bacterial inner membrane via the SecY channel.

Purpose of the Study:

• To elucidate the mechanism by which SecA translocates polypeptide chains through the SecY channel.
• To provide structural insights into the active SecA-SecY translocon during protein translocation.

Main Methods:

• Electron cryomicroscopy (cryo-EM) was used to determine the structures of the SecA-SecY translocon.
• Structures were captured with a polypeptide substrate in the presence of different nucleotides and analogs.

Main Results:

• Cryo-EM structures revealed SecA-SecY translocon complexes with polypeptide substrates in various translocation states.
• SecA undergoes nucleotide-dependent conformational changes, actively pushing the polypeptide substrate towards the SecY channel.
• The translocation mechanism shares similarities with RecA-like helicases and ribosome-mediated cotranslational translocation.

Conclusions:

• SecA utilizes ATP hydrolysis to generate mechanical force for polypeptide translocation through the SecY channel.
• The structural mechanism of SecA-mediated translocation is conserved across different protein translocation pathways.