F-box domain, Skp2-like <p>This entry represents the F-box domain, including:<ul> <li>Skp2 F-box [<cite idref="PUB00039397"/>]</li><li>Cdc4 F-box and linker domains [<cite idref="PUB00029039"/>]</li><li>F-box/WD-repeat protein 1 (beta-TRCP1) [<cite idref="PUB00029694"/>]</li><li>F-box/WD repeat-containing protein 7, FBXW7 [<cite idref="PUB00042288"/>]</li> </ul> </p><p>SCF complexes are four-subunit RING-type E3 ubiquitin ligases that bring together E2-thioester ubiquitin with unique adaptor proteins that specifically recognise proteins targeted for ubiquitin modification. Each SCF complex includes an F box protein, a cullin subunit, an adaptor protein, and a zinc RING finger protein. F box proteins are named for the conserved F box element found within each member, a small region of protein required for interaction with the Skp1 adaptor. The recently determined SCFSkp2 structure reveals a multisubunit complex comprised by the F box element of Skp2 (the protein responsible for substrate recruitment), Skp1 (the adaptor between Skp2 and Cul1), Cul1 (the bridge), and Rbx1 (the E3-like RING finger motif) [<cite idref="PUB00010627"/>]. The structure of the Skp1-Skp2 complex resembles a sickle, with Skp1 and the Skp2 F-box representing the handle and the LRR domain representing the curved blade [<cite idref="PUB00010628"/>]. Skp1 has a 125-residue N-terminal domain with an alpha/beta structure similar to that of the BTB/POZ domain fold, but with a helical insertion and a two-helix carboxy-terminal extension. The last two helices of the BTB/POZ fold and the two helices of the C-terminal extension form the Skp2-binding site. The structure of the Skp2 F-box consists of three helices, with the H1 helix packing orthogonally with the H2-H3 antiparallel helix pair. The 70-residue 'linker' following the F-box adopts the structure of three non-canonical LRRs that are contiguous with the seven LRRs predicted from the amino-acid sequence. The ten LRRs, each consisting of a beta-strand and an alpha-helix, pack into a curved structure. They form a single structural domain that is attached directly to the F-box. After the tenth LRR, the 30-residue C-terminal tail of Skp2 extends back toward the first LRR, packs loosely in the concave surface of the LRR domain and terminates in a short beta-strand inserted at the interface between Skp1 and Skp2.</p>