5IX1: Crystal Structure Of Mouse Morc3 Atpase-cw Cassette In Complex With Amppnp And H3k4me3 Peptide

Microrchidia (MORC) proteins are GHKL (gyrase, heat-shock protein 90, histidine kinase, MutL) ATPases that function in gene regulation in multiple organisms. Animal MORCs also contain CW-type zinc finger domains, which are known to bind to modified histones. We solved the crystal structure of the murine MORC3 ATPase-CW domain bound to the nucleotide analog AMPPNP (phosphoaminophosphonic acid-adenylate ester) and in complex with a trimethylated histone H3 lysine 4 (H3K4) peptide (H3K4me3). We observed that the MORC3 N-terminal ATPase domain forms a dimer when bound to AMPPNP. We used native mass spectrometry to show that dimerization is ATP-dependent, and that dimer formation is enhanced in the presence of nonhydrolyzable ATP analogs. The CW domain uses an aromatic cage to bind trimethylated Lys4 and forms extensive hydrogen bonds with the H3 tail. We found that MORC3 localizes to promoters marked by H3K4me3 throughout the genome, consistent with its binding to H3K4me3 in vitro. Our work sheds light on aspects of the molecular dynamics and function of MORC3.
PDB ID: 5IX1Download
MMDB ID: 142459
PDB Deposition Date: 2016/3/23
Updated in MMDB: 2016/09
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
Similar Structures:
Biological Unit for 5IX1: tetrameric; determined by author and by software (PISA)
Molecular Components in 5IX1
Label Count Molecule
Proteins (4 molecules)
Morc Family Cw-type Zinc Finger Protein 3(Gene symbol: Morc3)
Molecule annotation
Peptide From Histone H3.1(Gene symbol: Hist1h3g)
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

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