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Publication Abstract from PubMed

The 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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.