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3ebb
From Proteopedia
| 3ebb, resolution 1.90Å () | |||||||||
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| Gene: | PLAA, PLAP, FLJ11281, FLJ12699 (Homo sapiens) | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
PLAP/P97 complex
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.
Structure and function of the PLAA/Ufd3-p97/Cdc48 complex., Qiu L, Pashkova N, Walker JR, Winistorfer S, Allali-Hassani A, Akutsu M, Piper R, Dhe-Paganon S, J Biol Chem. 2010 Jan 1;285(1):365-72. Epub 2009 Nov 2. PMID:19887378
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
3EBB is a 8 chains structure with sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Qiu L, Pashkova N, Walker JR, 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. 2010 Jan 1;285(1):365-72. Epub 2009 Nov 2. PMID:19887378 doi:10.1074/jbc.M109.044685
Page seeded by OCA on Wed Feb 17 10:02:57 2010
Categories: Homo sapiens | Akutsu, M. | Amaya, M F. | Arrowsmith, C H. | Bochkarev, A. | Bountra, C. | Dhe-Paganon, S. | Edwards, A M. | Li, Y. | Qiu, L. | SGC, Structural Genomics Consortium. | Slessarev, Y. | Walker, J R. | Weigelt, J. | Acetylation | Armadillo repeat | Atp-binding | Chaperone | Cytoplasm | Disease mutation | Lipid-binding | Nucleotide-binding | Nucleus | Phosphoprotein | Sgc | Structural genomics consortium | Transport | Ubl conjugation pathway | Wd repeat
