5BNX: Crystal Structure Of Human Mcm2 Hbd And Asf1b Chaperoning A Histone H3.3-h4 Dimer

During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase, chaperones histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3-H4 dimer. Mutational analyses show that the MCM2 HBD is required for MCM2-7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical histones H3-H4 as well as H3.3 and CENPA variants. The unique histone-binding mode of MCM2 thus endows the replicative helicase with ideal properties for recycling histones genome wide during DNA replication.
PDB ID: 5BNXDownload
MMDB ID: 130213
PDB Deposition Date: 2015/5/26
Updated in MMDB: 2015/08
Experimental Method:
x-ray diffraction
Resolution: 2.31  Å
Source Organism:
Similar Structures:
Biological Unit for 5BNX: tetrameric; determined by author and by software (PISA)
Molecular Components in 5BNX
Label Count Molecule
Proteins (4 molecules)
Histone H3.3(Gene symbol: H3F3A)
Molecule annotation
Histone H4(Gene symbol: HIST1H4I)
Molecule annotation
DNA Replication Licensing Factor Mcm2(Gene symbol: MCM2)
Molecule annotation
Histone Chaperone Asf1b(Gene symbol: ASF1B)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB