5HDW

ApaG Domain of FBxo3

Summary for 5HDW

• Entry DOI: 10.2210/pdb5hdw/pdb
• Descriptor: F-box only protein 3 (2 entities in total)
• Functional Keywords: fbxo3, f-box, apag, fbxl2, protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 15241.23

Authors

Krzysiak, T.C.,Chen, B.B.,Mallampalli, R.K.,Gronenborn, A.M. (deposition date: 2016-01-05, release date: 2016-04-06, Last modification date: 2023-09-27)

Primary citation

Krzysiak, T.C.,Chen, B.B.,Lear, T.,Mallampalli, R.K.,Gronenborn, A.M.
Crystal structure and interaction studies of the human FBxo3 ApaG domain.
Febs J., 283:2091-2101, 2016

PubMed Abstract: Transcriptional activation of proinflammatory cytokines, mediated by tumor necrosis factor receptor-associated factors (TRAFs), is in part triggered by the degradation of the F-box protein, FBxl2, via an E3 ligase that contains another F-box protein, FBxo3. The ApaG domain of FBxo3 is required for the interaction with and degradation of FBxl2 [Mallampalli RK et al., (2013) J Immunol 191, 5247-5255]. Here, we report the X-ray structure of the human FBxo3 ApaG domain, residues 278-407, at 2.0 Å resolution. Like bacterial ApaG proteins, this domain is characterized by a classic Immunoglobin/Fibronectin III-type fold, comprising a seven-stranded β-sheet core, surrounded by four extended loops. Although cation binding had been proposed for bacterial ApaG proteins, no interactions with Mg(2+) or Co(2+) were detected for the human ApaG domain. In addition, dinucleotide polyphosphates, which have been reported to be second messengers in the inflammation response and targets of the bacterial apaG-containing operon, are not bound by the human ApaG domain. In the context of the full-length protein, loop 1, comprising residues 294-303, is critical for the interaction with FBxl2. However, titration of the individual ApaG domain with a 15-mer FBxl2 peptide that was phosphorylated on the crucial T404, as well as the inability of the ApaG domain to interact with full-length FBxl2, assessed by coimmunoprecipitation, indicate that the ApaG domain alone is necessary, but not sufficient for binding and degradation of FBxl2.

PubMed: 27010866
DOI: 10.1111/febs.13721

Experimental method

X-RAY DIFFRACTION (2 Å)