4OUH

Crystal structure of the FP domain of Human PI31 Proteasome Inhibitor

Summary for 4OUH

• Entry DOI: 10.2210/pdb4ouh/pdb
• Descriptor: Proteasome inhibitor PI31 subunit (2 entities in total)
• Functional Keywords: c-terminal extention alpha helix, proteasome inhibitor, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q92530
• Total number of polymer chains: 4
• Total formula weight: 72837.90

Authors

Shang, J.,Huang, X.,Du, Z. (deposition date: 2014-02-17, release date: 2015-02-25, Last modification date: 2024-02-28)

Primary citation

Shang, J.,Huang, X.,Du, Z.
The FP domains of PI31 and Fbxo7 have the same protein fold but very different modes of protein-protein interaction.
J.Biomol.Struct.Dyn., 33:1528-1538, 2015

PubMed 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.

PubMed: 25266262
DOI: 10.1080/07391102.2014.963675

Experimental method

X-RAY DIFFRACTION (2 Å)