PDBsum entry 5y0c

DNA binding protein/DNA

PDB id: 5y0c

Contents

Protein chains

96 a.a.

77 a.a.

108 a.a.

92 a.a.

87 a.a.

DNA/RNA

Metals

_MN ×10

_CL ×4

Waters ×392

PDB id:

5y0c

Name:

DNA binding protein/DNA

Title:

Crystal structure of the human nucleosome at 2.09 angstrom resolution

Structure:

DNA (146-mer). Chain: i, j. Engineered: yes. Histone h3.1. Chain: a, e. Synonym: histone h3/a,histone h3/b,histone h3/c,histone h3/d,histone h3/f,histone h3/h,histone h3/i,histone h3/j,histone h3/k,histone h3/l. Engineered: yes.

Source:

Homo sapiens. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Human. Gene: hist1h3a, h3fa, hist1h3b, h3fl, hist1h3c, h3fc, hist1h3d, h3fb, hist1h3e, h3fd, hist1h3f, h3fi, hist1h3g, h3fh, hist1h3h, h3fk, hist1h3i, h3ff, hist1h3j, h3fj. Expressed in: escherichia coli bl21(de3).

Resolution:

2.09Å R-factor: 0.203 R-free: 0.249

Authors:

H.Kurumizaka,Y.Arimura,R.Fujita,M.Noda

Key ref:

Y.Arimura et al. (2018). Cancer-associated mutations of histones H2B, H3.1 and H2A.Z.1 affect the structure and stability of the nucleosome. Nucleic Acids Res, 46, 10007-10018. PubMed id: 30053102

Date:

16-Jul-17 Release date: 18-Jul-18

Protein chains

P68431  (H31_HUMAN) -  Histone H3.1 from Homo sapiens

Seq: 136 a.a.

Struc: 96 a.a.

Protein chain

P62805  (H4_HUMAN) -  Histone H4 from Homo sapiens

Seq: 103 a.a.

Struc: 77 a.a.

Protein chains

P04908  (H2A1B_HUMAN) -  Histone H2A type 1-B/E from Homo sapiens

Seq: 130 a.a.

Struc: 108 a.a.

Protein chains

P06899  (H2B1J_HUMAN) -  Histone H2B type 1-J from Homo sapiens

Seq: 126 a.a.

Struc: 92 a.a.

Protein chain

P62805  (H4_HUMAN) -  Histone H4 from Homo sapiens

Seq: 103 a.a.

Struc: 87 a.a.

DNA/RNA chains

T-C-A-A-T-A-T-C-C-A-C-C-T-G-C-A-G-A-T-T-C-T-A-C-C-A-A-A-A-G-T-G-T-A-T-T-T-G-G- 145 bases

A-T-C-A-A-T-A-T-C-C-A-C-C-T-G-C-A-G-A-T-T-C-T-A-C-C-A-A-A-A-G-T-G-T-A-T-T-T-G- 146 bases

Nucleic Acids Res 46:10007-10018 (2018)

PubMed id: 30053102

Cancer-associated mutations of histones H2B, H3.1 and H2A.Z.1 affect the structure and stability of the nucleosome.

Y.Arimura, M.Ikura, R.Fujita, M.Noda, W.Kobayashi, N.Horikoshi, J.Sun, L.Shi, M.Kusakabe, M.Harata, Y.Ohkawa, S.Tashiro, H.Kimura, T.Ikura, H.Kurumizaka.

ABSTRACT

Mutations of the Glu76 residue of canonical histone H2B are frequently found in cancer cells. However, it is quite mysterious how a single amino acid substitution in one of the multiple H2B genes affects cell fate. Here we found that the H2B E76K mutation, in which Glu76 is replaced by Lys (E76K), distorted the interface between H2B and H4 in the nucleosome, as revealed by the crystal structure and induced nucleosome instability in vivo and in vitro. Exogenous production of the H2B E76K mutant robustly enhanced the colony formation ability of the expressing cells, indicating that the H2B E76K mutant has the potential to promote oncogenic transformation in the presence of wild-type H2B. We found that other cancer-associated mutations of histones, H3.1 E97K and H2A.Z.1 R80C, also induced nucleosome instability. Interestingly, like the H2B E76K mutant, the H3.1 E97K mutant was minimally incorporated into chromatin in cells, but it enhanced the colony formation ability. In contrast, the H2A.Z.1 R80C mutant was incorporated into chromatin in cells, and had minor effects on the colony formation ability of the cells. These characteristics of histones with cancer-associated mutations may provide important information toward understanding how the mutations promote cancer progression.