2VT8

Structure of a conserved dimerisation domain within Fbox7 and PI31

Summary for 2VT8

• Entry DOI: 10.2210/pdb2vt8/pdb
• Descriptor: PROTEASOME INHIBITOR PI31 SUBUNIT (2 entities in total)
• Functional Keywords: polymorphism, hydrolase inhibitor
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : Q92530
• Total number of polymer chains: 2
• Total formula weight: 34396.72

Authors

Kirk, R.J.,Murray-Rust, J.,Knowles, P.P.,Laman, H.,McDonald, N.Q. (deposition date: 2008-05-12, release date: 2008-05-20, Last modification date: 2024-05-01)

Primary citation

Kirk, R.J.,Laman, H.,Knowles, P.P.,Murray-Rust, J.,Lomonosov, M.,Meziane, E.K.,McDonald, N.Q.
Structure of a Conserved Dimerization Domain within the F-Box Protein Fbxo7 and the Pi31 Proteasome Inhibitor.
J.Biol.Chem., 283:22325-, 2008

PubMed Abstract: F-box proteins are the substrate-recognition components of the Skp1-Cul1-F box protein (SCF) E3 ubiquitin ligases. Here we report a structural relationship between Fbxo7, a component of the SCF(Fbxo7) E3 ligase, and the proteasome inhibitor PI31. SCF(Fbxo7) is known to catalyze the ubiquitination of hepatoma-up-regulated protein (HURP) and the inhibitor of apoptosis (IAP) protein but also functions as an activator of cyclin D-Cdk6 complexes. We identify PI31 as an Fbxo7.Skp1 binding partner and show that this interaction requires an N-terminal domain present in both proteins that we term the FP (Fbxo7/PI31) domain. The crystal structure of the PI31 FP domain reveals a novel alpha/beta-fold. Biophysical and mutational analyses are used to map regions of the PI31 FP domain mediating homodimerization and required for heterodimerization with Fbxo7.Skp1. Equivalent mutations in Fbxo7 ablate interaction with PI31 and also block Fbxo7 homodimerization. Knockdown of Fbxo7 does not affect PI31 levels arguing against PI31 being a substrate for SCF(Fbxo7). We present a model for FP domain-mediated dimerization of SCF(Fbxo7) and PI31.

PubMed: 18495667
DOI: 10.1074/JBC.M709900200

Experimental method

X-RAY DIFFRACTION (2.6 Å)