5ix1
From Proteopedia
Crystal structure of mouse Morc3 ATPase-CW cassette in complex with AMPPNP and H3K4me3 peptide
Structural highlights
FunctionMORC3_MOUSE Nuclear factor which forms MORC3-NBs (nuclear bodies) via an ATP-dependent mechanism (By similarity). Sumoylated MORC3-NBs can also associate with PML-NBs (By similarity). Recruits TP53 and SP100 to PML-NBs, thus regulating TP53 activity (PubMed:17332504). Binds RNA in vitro (By similarity).[UniProtKB:Q14149][1] Publication Abstract from PubMedMicrorchidia (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. Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin.,Li S, Yen L, Pastor WA, Johnston JB, Du J, Shew CJ, Liu W, Ho J, Stender B, Clark AT, Burlingame AL, Daxinger L, Patel DJ, Jacobsen SE Proc Natl Acad Sci U S A. 2016 Aug 30;113(35):E5108-16. doi:, 10.1073/pnas.1609709113. Epub 2016 Aug 15. PMID:27528681[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Large Structures | Mus musculus | Du J | Li S | Patel DJ