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Using In Vitro Fluorescence Resonance Energy Transfer to Study the Dynamics Of Protein Complexes at a Millisecond Time Scale
Published on: March 14, 2019
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Co-adaptor driven assembly of a CUL3 E3 ligase complex
David Akopian1, Colleen A McGourty1, Michael Rapé2
1Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley CA 94720, USA.
Molecular Cell
|February 5, 2022
Summary
Cullin-RING ligases (CRLs) assemble via substrate adaptors and cullins. A co-adaptor, PEF1-ALG2, initiates CRL3 formation and couples substrate recruitment to ubiquitylation, controlling development.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Cullin-RING ligases (CRLs) are crucial ubiquitylation enzymes.
- CRLs consist of a cullin scaffold and diverse substrate adaptors.
- The assembly of CRLs is essential for signal transduction but poorly understood.
Purpose of the Study:
- To investigate the regulation of CRL complex formation.
- To elucidate the role of co-adaptors in CRL assembly and function.
- To understand how CRL assembly is coupled to substrate recognition.
Main Methods:
- Utilized CUL3KLHL12 as a model system.
- Investigated the function of the co-adaptor PEF1-ALG2.
- Examined the process of CRL3 formation and stabilization.
Main Results:
- PEF1-ALG2 initiates CRL3 formation by releasing KLHL12 from an inhibitor at the ER.
- Co-adaptor monoubiquitylation stabilizes the CRL3 enzyme.
- The co-adaptor links substrate recruitment to ubiquitylation.
Conclusions:
- CRL assembly is a tightly regulated process.
- Specific CRL regulators, like co-adaptors, cooperate with general adaptor exchange.
- This coordinated mechanism establishes E3 ligase complexes controlling metazoan development.
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