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Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses
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An inhibitory segment within G-patch activators tunes Prp43-ATPase activity during ribosome assembly
Daniela Portugal-Calisto1, Alexander Gregor Geiger1, Julius Rabl2
1Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
Nature Communications
|November 23, 2024
Summary
Researchers identified an inhibitory segment (I-patch) in Tma23 and Pxr1 that controls the RNA helicase Prp43 (DHX15) activity. This discovery provides insights into precise RNA remodeling during ribosome assembly.
Area of Science:
- Molecular Biology
- Biochemistry
- Structural Biology
Background:
- The ATP-dependent RNA helicase Prp43 (DHX15 in humans) is crucial for remodeling RNA:protein complexes.
- Understanding how activators like Tma23 and Pxr1 regulate Prp43 function is essential for comprehending ribosome assembly.
Purpose of the Study:
- To elucidate the mechanisms by which Tma23 and Pxr1 modulate the activity of the RNA helicase Prp43.
- To define the functional segments within Tma23 and Pxr1 that govern Prp43's role in ribosome biogenesis.
Main Methods:
- Comparative analysis of Tma23 and Pxr1 activators.
- Cryo-electron microscopy (Cryo-EM).
- Hydrogen-deuterium exchange mass spectrometry (HDX-MS).
Main Results:
- Identified an inhibitory segment (I-patch) in Tma23 and Pxr1 that restrains Prp43 ATPase activity.
- Demonstrated allosteric inhibition of Prp43 by I-patch binding to its catalytic domains via Cryo-EM and HDX-MS.
- Revealed dimerization segments in Tma23 and Pxr1 that facilitate the formation of higher-order Prp43 complexes.
Conclusions:
- Prp43 activity is coordinated by toggling interactions with activating (G-patch) and inhibitory (I-patch) segments of its activators.
- This regulated mechanism ensures controlled Prp43 activation for precise RNA remodeling during ribosome formation.
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