PDBsum entry 6pww

Histone binding/DNA binding/DNA

PDB id: 6pww

Contents

Protein chains

333 a.a.

303 a.a.

153 a.a.

98 a.a.

82 a.a.

107 a.a.

93 a.a.

DNA/RNA

Ligands

SAH

Metals

_ZN

PDB id:

6pww

Name:

Histone binding/DNA binding/DNA

Title:

Cryo-em structure of mll1 in complex with rbbp5 and wdr5 bound to the nucleosome

Structure:

Retinoblastoma-binding protein 5. Chain: a. Synonym: rbbp-5,retinoblastoma-binding protein rbq-3. Engineered: yes. Wd repeat-containing protein 5. Chain: b. Synonym: bmp2-induced 3-kb gene protein. Engineered: yes. Histone-lysine n-methyltransferase 2a.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rbbp5, rbq3. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: wdr5, big3. Gene: kmt2a, all1, cxxc7, hrx, htrx, mll, mll1, trx1. Xenopus laevis.

Authors:

S.H.Park,A.Ayoub,Y.T.Lee,J.Xu,W.Zhang,B.Zhang,Y.Zhang,M.A.Cianfrocco, M.Su,Y.Dou,U.Cho

Key ref:

S.H.Park et al. (2019). Cryo-EM structure of the human MLL1 core complex bound to the nucleosome. Nat Commun, 10, 5540. PubMed id: 31804488 DOI: 10.1038/s41467-019-13550-2

Date:

23-Jul-19 Release date: 18-Dec-19

Protein chain

Q15291  (RBBP5_HUMAN) -  Retinoblastoma-binding protein 5 from Homo sapiens

Seq: 538 a.a.

Struc: 333 a.a.

Protein chain

P61964  (WDR5_HUMAN) -  WD repeat-containing protein 5 from Homo sapiens

Seq: 334 a.a.

Struc: 303 a.a.

Protein chain

Q03164  (KMT2A_HUMAN) -  Histone-lysine N-methyltransferase 2A from Homo sapiens

Seq: 3969 a.a.

Struc: 153 a.a.*

Protein chains

P84233  (H32_XENLA) -  Histone H3.2 from Xenopus laevis

Seq: 136 a.a.

Struc: 98 a.a.*

Protein chains

P62799  (H4_XENLA) -  Histone H4 from Xenopus laevis

Seq: 103 a.a.

Struc: 82 a.a.

Protein chains

P06897  (H2A1_XENLA) -  Histone H2A type 1 from Xenopus laevis

Seq: 130 a.a.

Struc: 107 a.a.*

Protein chains

P02281  (H2B11_XENLA) -  Histone H2B 1.1 from Xenopus laevis

Seq: 126 a.a.

Struc: 93 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DNA/RNA chains

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

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

Enzyme reactions

• Enzyme class 2: Chain C: E.C.2.1.1.- - ?????
• Enzyme class 3: Chain C: E.C.2.1.1.364 - [histone H3]-lysine(4) N-methyltransferase.
• Reaction: L-lysyl₄-[histone H3] + S-adenosyl-L-methionine = N₆-methyl-L- lysyl₄-[histone H3] + S-adenosyl-L-homocysteine + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1038/s41467-019-13550-2

Nat Commun 10:5540 (2019)

PubMed id: 31804488

Cryo-EM structure of the human MLL1 core complex bound to the nucleosome.

S.H.Park, A.Ayoub, Y.T.Lee, J.Xu, H.Kim, W.Zheng, B.Zhang, L.Sha, S.An, Y.Zhang, M.A.Cianfrocco, M.Su, Y.Dou, U.S.Cho.

ABSTRACT

Mixed lineage leukemia (MLL) family histone methyltransferases are enzymes that deposit histone H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive structural and biochemical studies, the molecular mechanisms whereby the MLL complexes recognize histone H3K4 within nucleosome core particles (NCPs) remain unclear. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the NCP-bound human MLL1 core complex. We show that the MLL1 core complex anchors to the NCP via the conserved RbBP5 and ASH2L, which interact extensively with nucleosomal DNA and the surface close to the N-terminal tail of histone H4. Concurrent interactions of RbBP5 and ASH2L with the NCP uniquely align the catalytic MLL1^SET domain at the nucleosome dyad, thereby facilitating symmetrical access to both H3K4 substrates within the NCP. Our study sheds light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.