3ebb › Citations

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 285 365-72 (2010)
Cited: 23 times
EuropePMC logo PMID: 19887378

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.

Reviews - 3ebb mentioned but not cited (3)

  1. Structure and function of the AAA+ ATPase p97/Cdc48p. Xia D, Tang WK, Ye Y. Gene 583 64-77 (2016)
  2. A Mighty "Protein Extractor" of the Cell: Structure and Function of the p97/CDC48 ATPase. Ye Y, Tang WK, Zhang T, Xia D. Front Mol Biosci 4 39 (2017)
  3. Structural insights of the p97/VCP AAA+ ATPase: How adapter interactions coordinate diverse cellular functionality. Braxton JR, Southworth DR. J Biol Chem 299 105182 (2023)

Articles - 3ebb mentioned but not cited (3)

  1. 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. 285 365-372 (2010)
  2. Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy. Falik Zaccai TC, Savitzki D, Zivony-Elboum Y, Vilboux T, Fitts EC, Shoval Y, Kalfon L, Samra N, Keren Z, Gross B, Chasnyk N, Straussberg R, Mullikin JC, Teer JK, Geiger D, Kornitzer D, Bitterman-Deutsch O, Samson AO, Wakamiya M, Peterson JW, Kirtley ML, Pinchuk IV, Baze WB, Gahl WA, Kleta R, Anikster Y, Chopra AK. Brain 140 370-386 (2017)
  3. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)


Reviews citing this publication (7)

  1. The power of AAA-ATPases on the road of pre-60S ribosome maturation--molecular machines that strip pre-ribosomal particles. Kressler D, Hurt E, Bergler H, Bassler J. Biochim. Biophys. Acta 1823 92-100 (2012)
  2. Control of p97 function by cofactor binding. Buchberger A, Schindelin H, Hänzelmann P. FEBS Lett. 589 2578-2589 (2015)
  3. The AAA+ ATPase p97, a cellular multitool. Stach L, Freemont PS. Biochem. J. 474 2953-2976 (2017)
  4. The Interplay of Cofactor Interactions and Post-translational Modifications in the Regulation of the AAA+ ATPase p97. Hänzelmann P, Schindelin H. Front Mol Biosci 4 21 (2017)
  5. Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes. Saffert P, Enenkel C, Wendler P. Front Mol Biosci 4 33 (2017)
  6. Emerging mechanistic insights into AAA complexes regulating proteasomal degradation. Förster F, Schuller JM, Unverdorben P, Aufderheide A. Biomolecules 4 774-794 (2014)
  7. Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases. Chu S, Xie X, Payan C, Stochaj U. Mol Neurodegener 18 52 (2023)

Articles citing this publication (10)

  1. WD40 repeat propellers define a ubiquitin-binding domain that regulates turnover of F box proteins. Pashkova N, Gakhar L, Winistorfer SC, Yu L, Ramaswamy S, Piper RC. Mol. Cell 40 433-443 (2010)
  2. Cellular functions of Ufd2 and Ufd3 in proteasomal protein degradation depend on Cdc48 binding. Böhm S, Lamberti G, Fernández-Sáiz V, Stapf C, Buchberger A. Mol. Cell. Biol. 31 1528-1539 (2011)
  3. Doa1 targets ubiquitinated substrates for mitochondria-associated degradation. Wu X, Li L, Jiang H. J. Cell Biol. 213 49-63 (2016)
  4. Ubiquitin-proteasome genes as targets for modulation of cisplatin sensitivity in fission yeast. Gatti L, Hoe KL, Hayles J, Righetti SC, Carenini N, Bo LD, Kim DU, Park HO, Perego P. BMC Genomics 12 44 (2011)
  5. Structural Details of Ufd1 Binding to p97 and Their Functional Implications in ER-Associated Degradation. Le LT, Kang W, Kim JY, Le OT, Lee SY, Yang JK. PLoS ONE 11 e0163394 (2016)
  6. Molecular determinants of the interaction between Doa1 and Hse1 involved in endosomal sorting. Han S, Shin D, Choi H, Lee S. Biochem. Biophys. Res. Commun. 446 352-357 (2014)
  7. Doa1 is a MAD adaptor for Cdc48. Zhang T, Ye Y. J. Cell Biol. 213 7-9 (2016)
  8. Interaction between the AAA ATPase p97/VCP and a concealed UBX domain in the copper transporter ATP7A is associated with motor neuron degeneration. Yi L, Kaler SG. J. Biol. Chem. 293 7606-7617 (2018)
  9. PTP4A2 promotes lysophagy by dephosphorylation of VCP/p97 at Tyr805. Bai Y, Yu G, Zhou HM, Amarasinghe O, Zhou Y, Zhu P, Li Q, Zhang L, Nguele Meke F, Miao Y, Chapman E, Tao WA, Zhang ZY. Autophagy 19 1562-1581 (2023)
  10. Phospho-Ser784-VCP Is Required for DNA Damage Response and Is Associated with Poor Prognosis of Chemotherapy-Treated Breast Cancer. Zhu C, Rogers A, Asleh K, Won J, Gao D, Leung S, Li S, Vij KR, Zhu J, Held JM, You Z, Nielsen TO, Shao J. Cell Rep 31 107745 (2020)


Quick links