Crystal Structures of Histone and p53 Methyltransferase SmyD2
Author Information
Author(s): Jiang Yuanyuan, Sirinupong Nualpun, Brunzelle Joseph, Yang Zhe
Primary Institution: Wayne State University School of Medicine
Hypothesis
The methyltransferase activity of SmyD proteins is regulated by autoinhibition via the intra- and interdomain bending of the conserved C-terminal domain (CTD).
Conclusion
The study provides the first evidence for the intradomain flexibility of the TPR-like CTD in SmyD2, which may be important for the activation of SmyD proteins by Hsp90.
Supporting Evidence
- SmyD2 can methylate non-histone targets including p53 and the retinoblastoma tumor suppressor.
- The structures reveal that the CTD is structurally similar to tetratricopeptide repeats (TPR).
- Two crystal structures of SmyD2 were determined at 2.1 Å and 1.8 Å.
- The study shows significant differences in the first two helices of the CTDs between different SmyD2 structures.
Takeaway
SmyD2 is a protein that helps control gene expression and can change shape to allow it to work better, especially when helped by another protein called Hsp90.
Methodology
The study involved determining the crystal structures of SmyD2 in complex with the cofactor product S-adenosylhomocysteine and the inhibitor sinefungin using X-ray diffraction.
Limitations
The study does not provide in vivo evidence for the proposed mechanisms of SmyD2 activation.
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website