5WVO

Crystal structure of DNMT1 RFTS domain in complex with K18/K23 mono-ubiquitylated histone H3

Summary for 5WVO

• Entry DOI: 10.2210/pdb5wvo/pdb
• Descriptor: Ubiquitin, DNA (cytosine-5)-methyltransferase 1, Histone H3.1, ... (5 entities in total)
• Functional Keywords: dna methylation, ubiquitination, signaling protein-transferase complex, signaling protein/transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Ubiquitin: Cytoplasm : P62979; Nucleus : P26358 P68431
• Total number of polymer chains: 4
• Total formula weight: 49116.05

Authors

Ishiyama, S.,Nishiyama, A.,Nakanishi, M.,Arita, K. (deposition date: 2016-12-28, release date: 2017-11-15, Last modification date: 2024-10-23)

Primary citation

Ishiyama, S.,Nishiyama, A.,Saeki, Y.,Moritsugu, K.,Morimoto, D.,Yamaguchi, L.,Arai, N.,Matsumura, R.,Kawakami, T.,Mishima, Y.,Hojo, H.,Shimamura, S.,Ishikawa, F.,Tajima, S.,Tanaka, K.,Ariyoshi, M.,Shirakawa, M.,Ikeguchi, M.,Kidera, A.,Suetake, I.,Arita, K.,Nakanishi, M.
Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance
Mol. Cell, 68:350-360.e7, 2017

PubMed Abstract: The proper location and timing of Dnmt1 activation are essential for DNA methylation maintenance. We demonstrate here that Dnmt1 utilizes two-mono-ubiquitylated histone H3 as a unique ubiquitin mark for its recruitment to and activation at DNA methylation sites. The crystal structure of the replication foci targeting sequence (RFTS) of Dnmt1 in complex with H3-K18Ub/23Ub reveals striking differences to the known ubiquitin-recognition structures. The two ubiquitins are simultaneously bound to the RFTS with a combination of canonical hydrophobic and atypical hydrophilic interactions. The C-lobe of RFTS, together with the K23Ub surface, also recognizes the N-terminal tail of H3. The binding of H3-K18Ub/23Ub results in spatial rearrangement of two lobes in the RFTS, suggesting the opening of its active site. Actually, incubation of Dnmt1 with H3-K18Ub/23Ub increases its catalytic activity in vitro. Our results therefore shed light on the essential role of a unique ubiquitin-binding module in DNA methylation maintenance.

PubMed: 29053958
DOI: 10.1016/j.molcel.2017.09.037

Experimental method

X-RAY DIFFRACTION (1.997 Å)