PDBsum entry 4s3o

Ligase/transcription

PDB id: 4s3o

Contents

Protein chains

148 a.a.

105 a.a.

99 a.a.

95 a.a.

95 a.a.

Metals

_ZN ×8

Waters ×153

PDB id:

4s3o

Name:

Ligase/transcription

Title:

Pcgf5-ring1b-ubch5c complex

Structure:

Ubiquitin-conjugating enzyme e2 d3. Chain: a, d. Synonym: ubiquitin carrier protein d3, ubiquitin-conjugating enzyme e2(17)kb 3, ubiquitin-conjugating enzyme e2-17 kda 3, ubiquitin- protein ligase d3. Engineered: yes. E3 ubiquitin-protein ligase ring2. Chain: b, e. Fragment: ring domain, unp residues 1-116.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ube2d3, ubc5c, ubch5c. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: rnf2, bap1, ding, hipi3, ring1b. Gene: pcgf5, rnf159. Expression_system_taxid: 562

Resolution:

2.00Å R-factor: 0.196 R-free: 0.237

Authors:

A.M.Taherbhoy,A.G.Cochran

Key ref:

A.M.Taherbhoy et al. (2015). BMI1-RING1B is an autoinhibited RING E3 ubiquitin ligase. Nat Commun, 6, 7621. PubMed id: 26151332 DOI: 10.1038/ncomms8621

Date:

23-Mar-15 Release date: 15-Jul-15

Protein chains

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

Seq: 147 a.a.

Struc: 148 a.a.*

Protein chain

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

Seq: 336 a.a.

Struc: 105 a.a.

Protein chain

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

Seq: 336 a.a.

Struc: 99 a.a.

Protein chain

Q86SE9  (PCGF5_HUMAN) -  Polycomb group RING finger protein 5 from Homo sapiens

Seq: 256 a.a.

Struc: 95 a.a.

Protein chain

Q86SE9  (PCGF5_HUMAN) -  Polycomb group RING finger protein 5 from Homo sapiens

Seq: 256 a.a.

Struc: 95 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 2: Chains A, D: 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 A, D: 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 B, E: 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
• Enzyme class 5: Chains C, F: E.C.?

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/ncomms8621

Nat Commun 6:7621 (2015)

PubMed id: 26151332

BMI1-RING1B is an autoinhibited RING E3 ubiquitin ligase.

A.M.Taherbhoy, O.W.Huang, A.G.Cochran.

ABSTRACT

Polycomb repressive complex 1 (PRC1) is required for ubiquitination of histone H2A lysine 119, an epigenetic mark associated with repression of genes important in developmental regulation. The E3 ligase activity of PRC1 resides in the RING1A/B subunit when paired with one of six PCGF partners. The best known of these is the oncogene BMI1/PCGF4. We find that canonical PRC1 E3 ligases such as PCGF4-RING1B have intrinsically very low enzymatic activity compared with non-canonical PRC1 RING dimers. The structure of a high-activity variant in complex with E2 (PCGF5-RING1B-UbcH5c) reveals only subtle differences from an earlier PCGF4 complex structure. However, two charged residues present in the modelled interface with E2-conjugated ubiquitin prove critical: in BMI1/PCGF4, these residues form a salt bridge that may limit efficient ubiquitin transfer. The intrinsically low activity of the PCGF4-RING1B heterodimer is offset by a relatively favourable interaction with nucleosome substrates, resulting in an efficient site-specific monoubiquitination.