PDBsum entry 3l2o

Protein binding/cell cycle

PDB id: 3l2o

Contents

Protein chains

145 a.a. *

274 a.a. *

Waters ×76

* Residue conservation analysis

PDB id:

3l2o

Name:

Protein binding/cell cycle

Title:

Structure-based mechanism of dimerization-dependent ubiquitination by the scffbx4 ubiquitin ligase

Structure:

S-phase kinase-associated protein 1. Chain: a. Synonym: cyclin a/cdk2-associated protein p19, p19skp1, p19a, RNA polymerase ii elongation factor-like protein, organ of corti protein 2, ocp-2, ocp-ii, transcription elongation factor b, siii. Engineered: yes. Mutation: yes. F-box only protein 4. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: emc19, ocp2, skp1, skp1a, tceb1l. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: fbx4, fbxo4.

Resolution:

2.80Å R-factor: 0.252 R-free: 0.295

Authors:

Y.Li,B.Hao

Key ref:

Y.Li and B.Hao (2010). Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase. J Biol Chem, 285, 13896-13906. PubMed id: 20181953

Date:

15-Dec-09 Release date: 23-Feb-10

Protein chain

P63208  (SKP1_HUMAN) -  S-phase kinase-associated protein 1 from Homo sapiens

Seq: 163 a.a.

Struc: 145 a.a.*

Protein chain

Q9UKT5  (FBX4_HUMAN) -  F-box only protein 4 from Homo sapiens

Seq: 387 a.a.

Struc: 274 a.a.

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

J Biol Chem 285:13896-13906 (2010)

PubMed id: 20181953

Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase.

Y.Li, B.Hao.

ABSTRACT

The F-box proteins are the substrate recognition subunits of the SCF (Skp1-Cul1-Rbx1-F- box protein) ubiquitin ligase complexes that control the stability of numerous regulators in eukaryotic cells. Here we show that dimerization of the F-box protein Fbx4 is essential for SCF(Fbx4) (the superscript denotes the F-box protein) ubiquitination activity toward the telomere regulator Pin2 (also known as TRF1). The crystal structure of Fbx4 in complex with an adaptor protein Skp1 reveals an antiparallel dimer configuration in which the linker domain of Fbx4 interacts with the C-terminal substrate-binding domain of the other protomer, whereas the C-terminal domain of the protein adopts a compact alpha/beta fold distinct from those of known F-box proteins. Biochemical studies indicate that both the N-terminal domain and a loop connecting the linker and C-terminal domain of Fbx4 are critical for the dimerization and activation of the protein. Our findings provide a framework for understanding the role of F-box dimerization in the SCF-mediated ubiquitination reaction.