PDBsum entry 4r8p

Structural protein/DNA

PDB id: 4r8p

Contents

Protein chains

98 a.a.

86 a.a.

104 a.a.

95 a.a.

105 a.a.

254 a.a.

97 a.a.

DNA/RNA

Metals

_ZN ×8

PDB id:

4r8p

Name:

Structural protein/DNA

Title:

Crystal structure of the ring1b/bmi1/ubch5c prc1 ubiquitylation module bound to the nucleosome core particle

Structure:

Histone h3.2. Chain: a, e. Engineered: yes. Histone h4. Chain: b, f. Engineered: yes. Histone h2a. Chain: c, g. Engineered: yes.

Source:

Xenopus laevis. Clawed frog,common platanna,platanna. Organism_taxid: 8355. Gene: histone h3.2. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: histone h4. Gene: hist1h2aj, loc494591. Gene: histone h2b 1.1.

Resolution:

3.28Å R-factor: 0.199 R-free: 0.245

Authors:

R.K.Mcginty,R.C.Henrici,S.Tan

Key ref:

R.K.McGinty et al. (2014). Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. Nature, 514, 591-596. PubMed id: 25355358 DOI: 10.1038/nature13890

Date:

02-Sep-14 Release date: 05-Nov-14

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: 86 a.a.

Protein chains

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

Seq: 130 a.a.

Struc: 104 a.a.*

Protein chains

P02281  (H2B11_XENLA) -  Histone H2B 1.1 from Xenopus laevis

Seq: 126 a.a.

Struc: 95 a.a.*

Protein chain

P35226  (BMI1_HUMAN) -  Polycomb complex protein BMI-1 from Homo sapiens

Seq: 326 a.a.

Struc: 105 a.a.

Protein chains

P61077  (UB2D3_HUMAN) -  Ubiquitin-conjugating enzyme E2 D3 from Homo sapiens

Seq: 147 a.a.

Struc: 254 a.a.*

Protein chains

Q99496  (RING2_HUMAN) -  E3 ubiquitin-protein ligase RING2 from Homo sapiens

Seq: 336 a.a.

Struc: 254 a.a.*

Protein chain

P35226  (BMI1_HUMAN) -  Polycomb complex protein BMI-1 from Homo sapiens

Seq: 326 a.a.

Struc: 97 a.a.

* PDB and UniProt seqs differ at 144 residue positions (black crosses)

DNA/RNA chains

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-A- 144 bases

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-A- 145 bases

Enzyme reactions

• Enzyme class 1: Chains A, B, C, D, E, F, G, H, K, M: E.C.?
• Enzyme class 2: Chains L, N: E.C.2.3.2.23 - E2 ubiquitin-conjugating enzyme.
• Reaction: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L- cysteine
• Enzyme class 3: Chains L, N: E.C.2.3.2.24 - (E3-independent) E2 ubiquitin-conjugating enzyme.
• Reaction: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E1 ubiquitin-activating enzyme]-L-cysteine + N₆- monoubiquitinyl-[acceptor protein]-L-lysine
• Enzyme class 4: Chains L, N: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine

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.

DOI no: 10.1038/nature13890

Nature 514:591-596 (2014)

PubMed id: 25355358

Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome.

R.K.McGinty, R.C.Henrici, S.Tan.

ABSTRACT

The Polycomb group of epigenetic enzymes represses expression of developmentally regulated genes in many eukaryotes. This group includes the Polycomb repressive complex 1 (PRC1), which ubiquitylates nucleosomal histone H2A Lys 119 using its E3 ubiquitin ligase subunits, Ring1B and Bmi1, together with an E2 ubiquitin-conjugating enzyme, UbcH5c. However, the molecular mechanism of nucleosome substrate recognition by PRC1 or other chromatin enzymes is unclear. Here we present the crystal structure of the human Ring1B-Bmi1-UbcH5c E3-E2 complex (the PRC1 ubiquitylation module) bound to its nucleosome core particle substrate. The structure shows how a chromatin enzyme achieves substrate specificity by interacting with several nucleosome surfaces spatially distinct from the site of catalysis. Our structure further reveals an unexpected role for the ubiquitin E2 enzyme in substrate recognition, and provides insight into how the related histone H2A E3 ligase, BRCA1, interacts with and ubiquitylates the nucleosome.