| Structural highlights
Function
[NPL4_RAT] The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ubiquitylated proteins are directed into a large number of different cellular pathways through interactions with effector proteins that contain conserved ubiquitin binding motifs. Here, we report the solution structure and ubiquitin binding properties of one such motif, the Npl4 zinc finger or RanBP2/Nup358 zinc finger (NZF) domain. Npl4 NZF forms a compact module composed of four antiparallel beta-strands linked by three ordered loops. A single zinc ion is coordinated by four conserved cysteines from the first and third loops, which form two rubredoxin knuckles. Npl4 NZF binds specifically, but weakly, to free ubiquitin using a conserved 13TF14 dipeptide to interact with the "Ile-44" surface of ubiquitin. Our studies reveal the structure of this versatile class of protein binding domains and provide a means for identifying the subset of NZF domains likely to bind ubiquitin.
Structure and ubiquitin interactions of the conserved zinc finger domain of Npl4.,Wang B, Alam SL, Meyer HH, Payne M, Stemmler TL, Davis DR, Sundquist WI J Biol Chem. 2003 May 30;278(22):20225-34. Epub 2003 Mar 18. PMID:12644454[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Meyer HH, Shorter JG, Seemann J, Pappin D, Warren G. A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways. EMBO J. 2000 May 15;19(10):2181-92. PMID:10811609 doi:http://dx.doi.org/10.1093/emboj/19.10.2181
- ↑ Hetzer M, Meyer HH, Walther TC, Bilbao-Cortes D, Warren G, Mattaj IW. Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly. Nat Cell Biol. 2001 Dec;3(12):1086-91. PMID:11781570 doi:http://dx.doi.org/10.1038/ncb1201-1086
- ↑ Ye Y, Meyer HH, Rapoport TA. The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature. 2001 Dec 6;414(6864):652-6. PMID:11740563 doi:http://dx.doi.org/10.1038/414652a
- ↑ Cao K, Nakajima R, Meyer HH, Zheng Y. The AAA-ATPase Cdc48/p97 regulates spindle disassembly at the end of mitosis. Cell. 2003 Oct 31;115(3):355-67. PMID:14636562
- ↑ Meyer HH, Wang Y, Warren G. Direct binding of ubiquitin conjugates by the mammalian p97 adaptor complexes, p47 and Ufd1-Npl4. EMBO J. 2002 Nov 1;21(21):5645-52. PMID:12411482
- ↑ Wang B, Alam SL, Meyer HH, Payne M, Stemmler TL, Davis DR, Sundquist WI. Structure and ubiquitin interactions of the conserved zinc finger domain of Npl4. J Biol Chem. 2003 May 30;278(22):20225-34. Epub 2003 Mar 18. PMID:12644454 doi:10.1074/jbc.M300459200
- ↑ Wang B, Alam SL, Meyer HH, Payne M, Stemmler TL, Davis DR, Sundquist WI. Structure and ubiquitin interactions of the conserved zinc finger domain of Npl4. J Biol Chem. 2003 May 30;278(22):20225-34. Epub 2003 Mar 18. PMID:12644454 doi:10.1074/jbc.M300459200
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