Cryo-EM structures of the human Elongator complex at work
Nour-El-Hana Abbassi1,2, Marcin Jaciuk1, David Scherf3
1Małopolska Centre of Biotechnology (MCB), Jagiellonian University, Krakow, Poland.
Nature Communications
|May 15, 2024
Summary
The Elongator complex
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- The Elongator complex catalyzes tRNA modifications essential for protein synthesis.
- Understanding the human Elongator complex's structure and function is crucial but limited.
- tRNA modifications influence ribosomal speed and co-translational folding.
Purpose of the Study:
- To elucidate the structure and mechanism of the human Elongator complex (ELP123).
- To provide high-resolution structural insights into tRNA modification.
- To investigate the functional consequences of patient-derived mutations.
Main Methods:
- Cryo-electron microscopy (cryo-EM) at resolutions up to 2.9 Å.
- Functional analyses of the Elongator complex.
- Structural studies of ELP123 in complex with tRNA and cofactors.
Main Results:
- Determined cryo-EM structures of human ELP123 at four reaction stages.
- Revealed tRNA binding exposes U33, triggering acetyl-CoA hydrolysis.
- Identified conserved residues critical for U34 acetylation and characterized mutation effects.
Conclusions:
- Provided a high-resolution structural view of the human Elongator complex.
- Detailed the molecular mechanism of tRNA modification by Elongator.
- Offered insights into the functional impact of Elongator mutations.
