Database accession: MF7000385
Name: Se-Met Dpb4/Dpb3 complex
PDB ID: 5y27
Experimental method: X-ray (1.90 Å)
Assembly: Heterodimer
Source organism: Schizosaccharomyces pombe
Primary publication of the structure:
He H, Li Y, Dong Q, Chang AY, Gao F, Chi Z, Su M, Zhang F, Ban H, Martienssen R, Chen YH, Li F
Coordinated regulation of heterochromatin inheritance by Dpb3-Dpb4 complex.
(2017) Proc. Natl. Acad. Sci. U.S.A. 114: 12524-12529
PMID: 29109278
Abstract:
During DNA replication, chromatin is disrupted ahead of the replication fork, and epigenetic information must be restored behind the fork. How epigenetic marks are inherited through DNA replication remains poorly understood. Histone H3 lysine 9 (H3K9) methylation and histone hypoacetylation are conserved hallmarks of heterochromatin. We previously showed that the inheritance of H3K9 methylation during DNA replication depends on the catalytic subunit of DNA polymerase epsilon, Cdc20. Here we show that the histone-fold subunit of Pol epsilon, Dpb4, interacts an uncharacterized small histone-fold protein, SPCC16C4.22, to form a heterodimer in fission yeast. We demonstrate that SPCC16C4.22 is nonessential for viability and corresponds to the true ortholog of Dpb3. We further show that the Dpb3-Dpb4 dimer associates with histone deacetylases, chromatin remodelers, and histones and plays a crucial role in the inheritance of histone hypoacetylation in heterochromatin. We solve the 1.9-Å crystal structure of Dpb3-Dpb4 and reveal that they form the H2A-H2B-like dimer. Disruption of Dpb3-Dpb4 dimerization results in loss of heterochromatin silencing. Our findings reveal a link between histone deacetylation and H3K9 methylation and suggest a mechanism for how two processes are coordinated during replication. We propose that the Dpb3-Dpb4 heterodimer together with Cdc20 serves as a platform for the recruitment of chromatin modifiers and remodelers that mediate heterochromatin assembly during DNA replication, and ensure the faithful inheritance of epigenetic marks in heterochromatin.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
protein heterodimerization activity protein heterodimerization activity
Biological process:
CMG complex assembly CMG complex assembly
DNA strand elongation involved in mitotic DNA replication DNA strand elongation involved in mitotic DNA replication
DNA-templated DNA replication DNA-templated DNA replication
heterochromatin formation heterochromatin formation
Cellular component:
epsilon DNA polymerase complex epsilon DNA polymerase complex
nuclear replication fork nuclear replication fork
nucleus nucleus
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 2
Name: DNA polymerase epsilon subunit D
Source organism: Schizosaccharomyces pombe
Length: 210 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMNQDKSKETSELDDLALPRSIIMRLVKGVLPEKSLVQKEALKAMINSATLFVSFLTSASGEIATNNNRKILMPQDVLNALDEIEYPEFSKTLKKHLEAYELALKEKRLKLPNVSDVDNRKKAKIDAHDTTPLDEEKDELEEERIAEDIAQNEVEQNIDDVEDLEEVNDTLDANAESPQIETIHLTDATGNPIEDSSESDSEESLQLNDSS
UniProtKB AC: P87174 (positions: 9-106)
Coverage: 46%
Name: DNA polymerase epsilon subunit C
Source organism: Schizosaccharomyces pombe
Length: 87 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMEKTYGKTVLPLSRVKRIIKQDEDVHYCSNASALLISVATELFVEKLATEAYQLAKLQKRKGIRYRDVEDVVRKDDQFEFLSDLFSI
UniProtKB AC: C6Y4D0 (positions: 1-87)
Coverage: 100%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Histone-like transcription factor (CBF/NF-Y) and archaeal histone
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
Data on the GdmCl-induced unfolding and refolding transitions of the dimer (monitored by stopped-flow far UV CD) fitted to a two-state model (PMID:15313621).
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
Download this entry's XML file (.xml)
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