5BNX

Crystal structure of Human MCM2 HBD and ASF1b chaperoning a histone H3.3-H4 dimer

Summary for 5BNX

• Entry DOI: 10.2210/pdb5bnx/pdb
• Related: 5BNV 5BO0
• Descriptor: Histone H3.3, Histone H4, DNA replication licensing factor MCM2, ... (6 entities in total)
• Functional Keywords: dna replication, mcm2, asf1, h3.3-h4 dimer, chaperone-dna binding protein complex, chaperone/dna binding protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: P84243 P62805 P49736 Q9NVP2
• Total number of polymer chains: 4
• Total formula weight: 46157.29

Authors

Huang, H.,Patel, D.J. (deposition date: 2015-05-26, release date: 2015-06-17, Last modification date: 2024-03-06)

Primary citation

Huang, H.,Strmme, C.B.,Saredi, G.,Hodl, M.,Strandsby, A.,Gonzalez-Aguilera, C.,Chen, S.,Groth, A.,Patel, D.J.
A unique binding mode enables MCM2 to chaperone histones H3-H4 at replication forks.
Nat.Struct.Mol.Biol., 22:618-626, 2015

PubMed Abstract: 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.

PubMed: 26167883
DOI: 10.1038/nsmb.3055

Experimental method

X-RAY DIFFRACTION (2.305 Å)