4l9c › Citations

Structure of the FP domain of Fbxo7 reveals a novel mode of protein-protein interaction.

Shang J, Wang G, Yang Y, Huang X, Du Z
Acta Crystallogr D Biol Crystallogr 70 155-64 (2014)
Cited: 4 times
EuropePMC logo PMID: 24419388

Abstract

The FP (Fbxo7/PI31) domains found in the F-box protein Fbxo7 and the proteasome inhibitor PI31 mediate the homodimerization and heterodimerization of Fbxo7 and PI31. Fbxo7 is the substrate-recognition subunit of the SCF(Fbxo7) (Skp1-Cul1-F-box protein) E3 ubiquitin ligase that catalyzes the ubiquitination of hepatoma up-regulated protein (HURP) and inhibitor of apoptosis protein (IAP). Fbxo7 also interacts with proteins that are not substrates of the ubiquitin proteasome system, such as Cdk6 and PI31. Here, the crystal structure of the Fbxo7 FP domain is reported at 2.0 Å resolution. The Fbxo7 FP domain adopts an α/β-fold similar to that of the PI31 FP domain. However, an α-helix and three β-strands in the Fbxo7 FP domain are longer than their counterparts in the PI31 FP domain. The differences in these secondary-structural elements are spatially clustered to define a more structured and extended C-terminal end of the Fbxo7 FP domain. The two FP domains also differ substantially in the length and conformation of the longest connecting loop. More importantly, structural differences between the two FP domains lead to drastically different modes of inter-domain protein-protein interaction. The inter-domain interface of the Fbxo7 FP domain is defined by the α-helical surface in one protomer and the β-sheet surface in the other protomer, whereas for the PI31 domain it is defined by either the α-helical surfaces or the β-sheet surfaces in both protomers. The inter-domain interaction of the Fbxo7 FP domain is much more extensive, featuring a larger contact surface area, better shape complementarity and more hydrophobic and hydrogen-bonding interactions. The Fbxo7 FP domain also has the potential to bind two protein partners simultaneously using the α-helical and β-sheet surfaces. The results of this structural study provide critical insights into how Fbxo7 may dimerize (or multimerize) and interact with other regulatory proteins via the FP domain.

Articles - 4l9c mentioned but not cited (1)

  1. Chemical inhibition of FBXO7 reduces inflammation and confers neuroprotection by stabilizing the mitochondrial kinase PINK1. Liu Y, Lear TB, Verma M, Wang KZ, Otero PA, McKelvey AC, Dunn SR, Steer E, Bateman NW, Wu C, Jiang Y, Weathington NM, Rojas M, Chu CT, Chen BB, Mallampalli RK. JCI Insight 5 131834 (2020)


Reviews citing this publication (1)

  1. Spo0M: structure and function beyond regulation of sporulation. Vega-Cabrera LA, Wood CD, Pardo-López L. Curr Genet 64 17-23 (2018)

Articles citing this publication (2)

  1. Expression, purification and crystallization of the SKICH domain of human TAX1BP1. Yang Y, Wang G, Huang X, Du Z. Acta Crystallogr F Struct Biol Commun 70 619-623 (2014)
  2. The FP domains of PI31 and Fbxo7 have the same protein fold but very different modes of protein-protein interaction. Shang J, Huang X, Du Z. J Biomol Struct Dyn 33 1528-1538 (2015)


Quick links