3EBB

PLAP/P97 complex

Summary for 3EBB

• Entry DOI: 10.2210/pdb3ebb/pdb
• Descriptor: PHOSPHOLIPASE A2-ACTIVATING PROTEIN, TRANSITIONAL ENDOPLASMIC RETICULUM ATPASE (TER ATP, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: armadillo repeat, structural genomics consortium, sgc, wd repeat, atp-binding, disease mutation, lipid-binding, nucleotide-binding, nucleus, phosphoprotein, transport, ubl conjugation pathway, chaperone
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm, cytosol: P55072
• Total number of polymer chains: 8
• Total formula weight: 139391.80

Authors

Walker, J.R.,Qiu, L.,Akutsu, M.,Slessarev, Y.,Amaya, M.F.,Li, Y.,Bountra, C.,Weigelt, J.,Arrowsmith, C.H.,Edwards, A.M.,Bochkarev, A.,Dhe-Paganon, S.,Structural Genomics Consortium (SGC) (deposition date: 2008-08-27, release date: 2009-02-24, Last modification date: 2024-10-09)

Primary citation

Qiu, L.,Pashkova, N.,Walker, J.R.,Winistorfer, S.,Allali-Hassani, A.,Akutsu, M.,Piper, R.,Dhe-Paganon, S.
Structure and function of the PLAA/Ufd3-p97/Cdc48 complex.
J.Biol.Chem., 285:365-372, 2010

PubMed Abstract: PLAA (ortholog of yeast Doa1/Ufd3, also know as human PLAP or phospholipase A2-activating protein) has been implicated in a variety of disparate biological processes that involve the ubiquitin system. It is linked to the maintenance of ubiquitin levels, but the mechanism by which it accomplishes this is unclear. The C-terminal PUL (PLAP, Ufd3p, and Lub1p) domain of PLAA binds p97, an AAA ATPase, which among other functions helps transfer ubiquitinated proteins to the proteasome for degradation. In yeast, loss of Doa1 is suppressed by altering p97/Cdc48 function indicating that physical interaction between PLAA and p97 is functionally important. Although the overall regions of interaction between these proteins are known, the structural basis has been unavailable. We solved the high resolution crystal structure of the p97-PLAA complex showing that the PUL domain forms a 6-mer Armadillo-containing domain. Its N-terminal extension folds back onto the inner curvature forming a deep ridge that is positively charged with residues that are phylogenetically conserved. The C terminus of p97 binds in this ridge, where the side chain of p97-Tyr(805), implicated in phosphorylation-dependent regulation, is buried. Expressed in doa1Delta null cells, point mutants of the yeast ortholog Doa1 that disrupt this interaction display slightly reduced ubiquitin levels, but unlike doa1Delta null cells, showed only some of the growth phenotypes. These data suggest that the p97-PLAA interaction is important for a subset of PLAA-dependent biological processes and provides a framework to better understand the role of these complex molecules in the ubiquitin system.

PubMed: 19887378
DOI: 10.1074/jbc.M109.044685

Experimental method

X-RAY DIFFRACTION (1.9 Å)