Structure and assembly pathway of the ribosome quality control complex

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Ribosome-associated quality control (RQC) degrades aberrant proteins.
• Listerin ubiquitin ligase targets stalled 60S ribosomal subunits with nascent polypeptides.
• Mechanisms for Listerin's specificity remain unclear.

Purpose of the Study:

• To elucidate how Listerin specifically recognizes nascent chain-containing 60S ribosomal subunits.
• To investigate the role of nuclear export mediator factor (NEMF) in Listerin's function.

Main Methods:

• Cryo-electron microscopy (cryo-EM) at 3.6 Å resolution.
• Structural analysis of a 60S-Listerin-NEMF complex.
• Mutational analysis to assess protein interactions.

Main Results:

• NEMF binds simultaneously to the 60S subunit and peptidyl-tRNA, sensing nascent chain occupancy.
• NEMF recruits and stabilizes Listerin, while Listerin's RWD domain contacts the ribosome.
• A multivalent interaction network confers Listerin's specificity for stalled ribosomes.

Conclusions:

• NEMF is crucial for Listerin's specific targeting of nascent chain-containing 60S subunits.
• Listerin utilizes a novel avidity-based mechanism for client recognition in RQC.
• This study reveals a new principle in protein quality control client recognition.