3wso
From Proteopedia
Crystal structure of the Skp1-FBG3 complex
Structural highlights
Function[FBX44_HUMAN] Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. [SKP1_HUMAN] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.[1] [2] Publication Abstract from PubMedThe Skp1-Cul1-F-box protein (SCF) complex catalyzes protein ubiquitination in diverse cellular processes and is one of the best-characterized ubiquitin ligases. F-box proteins determine the substrate specificities of SCF ubiquitin ligases. Among these, Fbs1/FBG1/FBXO2, Fbs2/FBG2/FBXO6, and Fbs3/FBG5/FBXO27 recognize the N-glycans of glycoproteins, whereas FBG3/FBXO44 has no sugar-binding activity, despite the high sequence homology and conservation of the residues necessary for oligosaccharide binding between Fbs1-3 and FBG3. Here we determined the crystal structure of the Skp1-FBG3 complex at a resolution of 2.6 A. The substrate-binding domain of FBG3 is composed of a 10-stranded antiparallel beta-sandwich with three helices. Although the overall structure of FBG3 is similar to that of Fbs1, the residues that form the Fbs1 carbohydrate-binding pocket failed to be superposed with the corresponding residues of FBG3. Structure-based mutational analysis shows that distinct hydrogen bond networks of four FBG3 loops, i.e., beta2-beta3, beta5-beta6, beta7-beta8, and beta9-beta10, prevent the formation of the carbohydrate-binding pocket shown in Fbs1. The Structural Differences between a Glycoprotein Specific F-Box Protein Fbs1 and Its Homologous Protein FBG3.,Kumanomidou T, Nishio K, Takagi K, Nakagawa T, Suzuki A, Yamane T, Tokunaga F, Iwai K, Murakami A, Yoshida Y, Tanaka K, Mizushima T PLoS One. 2015 Oct 13;10(10):e0140366. doi: 10.1371/journal.pone.0140366., eCollection 2015. PMID:26460611[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Iwai, K | Kumanomidou, T | Mizushima, T | Murakami, A | Nakagawa, T | Nishio, K | Suzuki, A | Takagi, K | Tanaka, K | Tokunaga, F | Yamane, T | Yoshida, Y | F-box protein | Ligase | Scf ubiquitin ligase | Skp1
