5vmd
From Proteopedia
Crystal structure of UBR-box from UBR6 in a domain-swapping conformation
Structural highlights
Disease[FBX11_HUMAN] Vitiligo. Defects in FBXO11 may be a cause of diffuse large B-cell lymphoma by allowing the accumulation of BCL6, an oncoprotein that has a critical role in lymphomas.[1] Function[FBX11_HUMAN] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. The SCF(FBXO11) complex mediates ubiquitination and degradation of BCL6, thereby playing a role in the germinal center B-cells terminal differentiation toward memory B-cells and plasma cells. The SCF(FBXO11) complex also mediates ubiquitination and degradation of DTL, an important step for the regulation of TGF-beta signaling, cell migration and the timing of the cell-cycle progression and exit. Binds to and neddylates phosphorylated p53/TP53, inhibiting its transcriptional activity. SCF(FBXO11) does not seem to direct ubiquitination of p53/TP53.[2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe UBR-box is a 70-residue zinc finger domain present in the UBR family of E3 ubiquitin ligases that directly binds N-terminal degradation signals in substrate proteins. UBR6, also called FBXO11, is an UBR-box containing E3 ubiquitin ligase that does not bind N-terminal signals. Here, we present the crystal structure of the UBR-box domain from human UBR6. The dimeric crystal structure reveals a unique form of domain swapping mediated by zinc coordination, where three independent protein chains come together to regenerate the topology of the monomeric UBR-box fold. Analysis of the structure suggests that the absence of N-terminal residue binding arises from the lack of an amino acid binding pocket. Crystal structure of the UBR-box from UBR6/FBXO11 reveals domain swapping mediated by zinc binding.,Munoz-Escobar J, Kozlov G, Gehring K Protein Sci. 2017 Jul 10. doi: 10.1002/pro.3227. PMID:28691247[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Gehring, K | Kozlov, G | Munoz-Escobar, J | Domain swapping | Fbxo11 | Ligase | Ubr-box | Ubr6 | Zinc | Zinc finger
