title: The FP domains of PI31 and Fbxo7 have the same protein fold but very different modes of protein-protein interaction.
abstract: Fbxo7 and PI31 contain a conserved FP domain that mediates the homo-/hetero-dimerization of the proteins. The PI31 FP domain may also interact with the F-box motif in Fbxo7. The FP domain-mediated protein-protein interactions are important for the functions of Fbxo7 and PI31. The crystal structures of the Fbxo7 and PI31 FP domains were determined previously, showing that a C-terminal helix in the Fbxo7 FP domain was not present in the PI31 FP domain. Here, we determine the crystal structure of the PI31 FP domain using a longer protein construct. The structure is comparable to the Fbxo7 FP domain (including the C-terminal helix), indicating that the two FP domains share the same global fold. However, the FP domains also harbor their own characteristic structural features, mainly in the longest loop (which has a largely fixed conformation due to extensive hydrogen bonding and hydrophobic interactions) and the C-terminal end regions. The crystal structures also reveal fundamental differences in the modes of protein-protein interactions mediated by the two FP domains: the PI31 FP domain utilizes either an α interface or β interface for homodimeric interaction, whereas the Fbxo7 FP domain utilizes an αβ interface. We perform modeling studies to show that the domain-specific structural features may dictate specific modes of inter-domain interactions. We propose that a heterodimeric interaction would be mediated by an αβ interface consisting of the α-helical and β-sheet surfaces of the Fbxo7 and PI31 FP domains, respectively. We also discuss the structural/functional significance of various modes of FP domain-mediated protein-protein interactions.
authors.affiliation: a Department of Chemistry and Biochemistry , Southern Illinois University at Carbondale , Carbondale , IL 62901 , USA.
authors.forename: Jinsai
authors.initials: J
authors.lastname: Shang
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Huang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Du
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D044783:F-Box Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins; D016415:Sequence Alignment
chemical_list: D044783:F-Box Proteins; C489149:FBXO7 protein, human; C121623:PSMF1 protein, human; D011506:Proteins; D011994:Recombinant Proteins; D046988:Proteasome Endopeptidase Complex
keywords: F-box; FP domain; Fbxo7; PI31 proteasome inhibitor; SCF E3 ubiquitin ligases