5IX1

Crystal structure of mouse Morc3 ATPase-CW cassette in complex with AMPPNP and H3K4me3 peptide

Summary for 5IX1

• Entry DOI: 10.2210/pdb5ix1/pdb
• Related: 5IX2
• Descriptor: MORC family CW-type zinc finger protein 3, Peptide from Histone H3.1, ZINC ION, ... (6 entities in total)
• Functional Keywords: morc3, atpase, cw domain, h3k4me3, transcription
• Biological source: Mus musculus (Mouse); More
• Cellular location: Nucleus, nucleoplasm : F7BJB9; Nucleus: P68433
• Total number of polymer chains: 4
• Total formula weight: 108308.53

Authors

Li, S.,Du, J.,Patel, D.J. (deposition date: 2016-03-23, release date: 2016-08-17, Last modification date: 2016-09-14)

Primary citation

Li, S.,Yen, L.,Pastor, W.A.,Johnston, J.B.,Du, J.,Shew, C.J.,Liu, W.,Ho, J.,Stender, B.,Clark, A.T.,Burlingame, A.L.,Daxinger, L.,Patel, D.J.,Jacobsen, S.E.
Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin
Proc.Natl.Acad.Sci.USA, 113:E5108-E5116, 2016

PubMed Abstract: 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.

PubMed: 27528681
DOI: 10.1073/pnas.1609709113

Experimental method

X-RAY DIFFRACTION (2.6 Å)