RSS

PDB:1LDD

Protein Name

Ubiquitin ligase complex

Species

Saccharomyces cerevisiae (Baker's yeast)

Biological Context

Ubiquitin-dependent proteolysis regulates protein abundance and serves a central regulatory function in many biological processes. Ubiquitin is prepared for conjugation to other proteins by the ATP-dependent ubiquitin-activating enzyme (E1), which creates an activated ubiquitin that is transferred to one of a set of ubiquitin-conjugating (E2) enzymes. The E2 enzymes act in conjunction with accessory (E3) proteins. In the E2-E3 complex, called ubiquitin ligase, the E3 component binds to specific degradation signals in protein substrates, helping E2 to form a multiubiquitin chain linked to a lysine of the substrate protein. In this chain, the C-terminal residue of each ubiquitin is linked to a specific lysine of the next ubiquitin molecule, producing a linear series of ubiquitin-ubiquitin conjugates. It is this multiubiquitin chain on a target protein that is recognized by a specific receptor in the proteasome.The SCF (Skp1-Cullin-F-box protein) and SCF-like complexes are the largest family of ubiquitin-protein ligases (also known as E3s) and mediate the ubiquitination of diverse regulatory and signaling proteins. Two functionally distinct types of E3s have been identified to date. HECT-type E3s catalyse ubiquitination by first forming an E3-ubiquitin thioester intermediate, while RING-type E3s do not appear to form such an intermediate.

Structure Description

1ldd1ldd_x1ldd_y

The SCF complexes are RING-type E3s that consist of Cul1, Rbx1, Skp1 and a member of the F-box protein family. Rbx1, which contains the RING domain, and Cul1 form a catalytic core complex that recruits a cognate E2, the variable F-box protein subunit binds the substrate, and Skp1 serves as an adapter that links the F-box protein to Cul1. The 3.2 angstrom structure of the quaternary complex containing Cul1, Rbx1, Skp1 and the F-box of Skp2, and the 3.0 angstrom structure of the Cul1-Rbx1 complex was determined. In the complexed structure, Cul1 has a long stalk with a globular domain that binds the Ring finger protein Rbx1, forming an intermolecular beta-sheet. Thus, a two-subunit catalytic core is constructed, recruiting the ubiquitin-conjugating enzyme. The long stalk is composed of three repeats of a five-helix motif, and it binds the above Skp1-Fbox complex at the tip. Cul1 provides a rigid arc-shaped structure, in which the subunits of Skp1-Fbox and Rbx1 are included, and it spans about 110 A. From the structure, Cul1 is considered to position the substrate and the ubiquitin-conjugating enzyme correctly, contributing to catalysis. Mutational studies support this model. Ubiquitin, so named because it is "ubiquitous", is a protein consisting of 76 amino acid residues. Now the ubiquitin-proteasome system is known to related to Parkinson's disease, Alzheimer's disease, Down's syndrome, and so on.

Protein Data Bank (PDB)

References

Source

Zheng, N. Schulman, B.A. Song, L. Miller, J.J. Jeffrey, P.D. Wang, P. Chu, C. Koepp, D.M. Elledge, S.J. Pagano, M. Conaway, R.C. Conaway, J.W. Harper, J.W. Pavletich, N.P.; "Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex."; Nature; (2002) 416:703-709 PubMed:11961546.

Others

author: Naoyuki Miyazaki


Japanese version:PDB:1LDD