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Updated: May 17, 2026
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X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
Published on: May 13, 2020
Crystal structure of the human PRMT5:MEP50 complex
Stephen Antonysamy1, Zahid Bonday, Robert M Campbell
1Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
Summary
This study reveals the crystal structure of human PRMT5 complexed with MEP50, detailing their interaction and substrate recognition. This provides insights into protein arginine methyltransferase 5 (PRMT5) function in cellular processes.
Area of Science:
- Biochemistry and structural biology
- Molecular and cellular biology
Background:
- Protein arginine methyltransferases (PRMTs) are crucial enzymes regulating cellular processes like gene expression and signaling.
- PRMT5 specifically performs symmetric di-methylation of arginine residues, impacting cell growth and development.
- MEP50 (methylosome protein 50) is a key WD40 protein that forms a core component of PRMT5 complexes, mediating interactions.
Purpose of the Study:
- To determine the crystal structure of the human PRMT5-MEP50 complex.
- To elucidate the structural basis of substrate recognition and the interaction between PRMT5 and MEP50.
Main Methods:
- X-ray crystallography was employed to determine the structure of the human PRMT5-MEP50 complex.
- The complex was studied in the presence of an S-adenosylmethionine analog and a peptide substrate derived from histone H4.
Main Results:
- The crystal structure of a hetero-octameric complex comprising human PRMT5 and MEP50 was determined.
- The structure highlights close interactions between the WD40 protein MEP50 and the N-terminal domain of PRMT5.
- Key structural elements involved in substrate recognition by the PRMT5-MEP50 complex were identified.
Conclusions:
- The determined structure provides a detailed molecular understanding of the PRMT5-MEP50 complex.
- This structural information is vital for comprehending PRMT5's role in cellular functions and for potential therapeutic targeting.
