5SVI: MORC3 CW domain in complex with unmodified histone H3

MORC3 is linked to inflammatory myopathies and cancer; however, the precise role of MORC3 in normal cell physiology and disease remains poorly understood. Here, we present detailed genetic, biochemical, and structural analyses of MORC3. We demonstrate that MORC3 is significantly upregulated in Down syndrome and that genetic abnormalities in MORC3 are associated with cancer. The CW domain of MORC3 binds to the methylated histone H3K4 tail, and this interaction is essential for recruitment of MORC3 to chromatin and accumulation in nuclear bodies. We show that MORC3 possesses intrinsic ATPase activity that requires DNA, but it is negatively regulated by the CW domain, which interacts with the ATPase domain. Natively linked CW impedes binding of the ATPase domain to DNA, resulting in a decrease in the DNA-stimulated enzymatic activity. Collectively, our studies provide a molecular framework detailing MORC3 functions and suggest that its modulation may contribute to human disease.
PDB ID: 5SVIDownload
MMDB ID: 145670
PDB Deposition Date: 2016/8/6
Updated in MMDB: 2016/12
Experimental Method:
x-ray diffraction
Resolution: 1.613  Å
Source Organism:
Heterocephalus glaber
Similar Structures:
Biological Unit for 5SVI: dimeric; determined by author and by software (PISA)
Molecular Components in 5SVI
Label Count Molecule
Proteins (2 molecules)
Morc Family Cw-type Zinc Finger Protein 3(Gene symbol: MORC3)
Molecule annotation
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB