3ebb: Difference between revisions

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<StructureSection load='3ebb' size='340' side='right'caption='[[3ebb]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
<StructureSection load='3ebb' size='340' side='right'caption='[[3ebb]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3ebb]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EBB FirstGlance]. <br>
<table><tr><td colspan='2'>[[3ebb]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EBB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EBB FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLAA, PLAP, FLJ11281, FLJ12699 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ebb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ebb OCA], [https://pdbe.org/3ebb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ebb RCSB], [https://www.ebi.ac.uk/pdbsum/3ebb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ebb ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ebb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ebb OCA], [https://pdbe.org/3ebb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ebb RCSB], [https://www.ebi.ac.uk/pdbsum/3ebb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ebb ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/TERA_HUMAN TERA_HUMAN]] Defects in VCP are the cause of inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD) [MIM:[https://omim.org/entry/167320 167320]]; also known as muscular dystrophy, limb-girdle, with Paget disease of bone or pagetoid amyotrophic lateral sclerosis or pagetoid neuroskeletal syndrome or lower motor neuron degeneration with Paget-like bone disease. IBMPFD features adult-onset proximal and distal muscle weakness (clinically resembling limb girdle muscular dystrophy), early-onset Paget disease of bone in most cases and premature frontotemporal dementia.<ref>PMID:20512113</ref> <ref>PMID:15034582</ref> <ref>PMID:15732117</ref> <ref>PMID:16247064</ref> <ref>PMID:16321991</ref>  Defects in VCP are the cause of amyotrophic lateral sclerosis type 14 with or without frontotemporal dementia (ALS14) [MIM:[https://omim.org/entry/613954 613954]]. ALS14 is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS14 may develop frontotemporal dementia.<ref>PMID:21145000</ref> 
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/PLAP_HUMAN PLAP_HUMAN]] Involved in the maintenance of ubiquitin levels (By similarity). [[https://www.uniprot.org/uniprot/TERA_HUMAN TERA_HUMAN]] Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. 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. Regulates E3 ubiquitin-protein ligase activity of RNF19A (By similarity). Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites. Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage.<ref>PMID:15456787</ref> <ref>PMID:16168377</ref> <ref>PMID:22020440</ref> <ref>PMID:22120668</ref> <ref>PMID:22607976</ref> <ref>PMID:23042607</ref> <ref>PMID:23042605</ref> 
[https://www.uniprot.org/uniprot/PLAP_HUMAN PLAP_HUMAN] Involved in the maintenance of ubiquitin levels (By similarity).
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eb/3ebb_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eb/3ebb_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Akutsu, M]]
[[Category: Akutsu M]]
[[Category: Amaya, M F]]
[[Category: Amaya MF]]
[[Category: Arrowsmith, C H]]
[[Category: Arrowsmith CH]]
[[Category: Bochkarev, A]]
[[Category: Bochkarev A]]
[[Category: Bountra, C]]
[[Category: Bountra C]]
[[Category: Dhe-Paganon, S]]
[[Category: Dhe-Paganon S]]
[[Category: Edwards, A M]]
[[Category: Edwards AM]]
[[Category: Li, Y]]
[[Category: Li Y]]
[[Category: Qiu, L]]
[[Category: Qiu L]]
[[Category: Structural genomic]]
[[Category: Slessarev Y]]
[[Category: Slessarev, Y]]
[[Category: Walker JR]]
[[Category: Walker, J R]]
[[Category: Weigelt J]]
[[Category: Weigelt, J]]
[[Category: Armadillo repeat]]
[[Category: Atp-binding]]
[[Category: Chaperone]]
[[Category: Disease mutation]]
[[Category: Lipid-binding]]
[[Category: Nucleotide-binding]]
[[Category: Nucleus]]
[[Category: Phosphoprotein]]
[[Category: Sgc]]
[[Category: Transport]]
[[Category: Ubl conjugation pathway]]
[[Category: Wd repeat]]

Latest revision as of 10:56, 9 October 2024

PLAP/P97 complexPLAP/P97 complex

Structural highlights

3ebb is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.9Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PLAP_HUMAN Involved in the maintenance of ubiquitin levels (By similarity).

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

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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ 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

3ebb, resolution 1.90Å

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