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GTP binding controls complex formation by the human ROCO protein MASL1
Sybille Dihanich1, Laura Civiero, Claudia Manzoni
1Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
The FEBS Journal
|November 30, 2013
Summary
Malignant fibrous histiocytoma amplified sequences with leucine-rich tandem repeats 1 (MASL1) binds GTP via its ROC domain, influencing its cellular complexes and toxicity. GTP binding regulates MASL1 complex formation and reduces its cellular toxicity.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- ROCO proteins, including LRRK1/2 and DAPK1, possess a ROC-COR supra-domain.
- The GTPase activity of the ROC domain in LRRK1/2 and DAPK1 is known, but its cellular implications remain unclear.
Purpose of the Study:
- To biochemically characterize malignant fibrous histiocytoma amplified sequences with leucine-rich tandem repeats 1 (MASL1).
- To investigate the impact of GTP binding on MASL1 complex formation and cellular function.
Main Methods:
- Biochemical assays to characterize MASL1.
- Analysis of MASL1 complex formation in the presence and absence of GTP.
- Cellular toxicity assays.
Main Results:
- MASL1 binds guanosine nucleotides through its ROC domain, similar to other ROCO proteins.
- MASL1 forms two distinct cellular complexes associated with heat shock protein 60.
- GTP binding modulates the formation of a low molecular weight MASL1 pool and reduces MASL1-induced cellular toxicity.
Conclusions:
- The ROC/GTPase domain of MASL1 plays a critical role in regulating its cellular function.
- GTP binding is a key modulator of MASL1 complex dynamics and cellular toxicity.
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