2w50

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[[Image:2w50.png|left|200px]]
 
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{{STRUCTURE_2w50| PDB=2w50 | SCENE= }}
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==N-terminal domain of human conserved dopamine neurotrophic factor (CDNF)==
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<StructureSection load='2w50' size='340' side='right'caption='[[2w50]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2w50]] is a 2 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=2W50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W50 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2w50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w50 OCA], [https://pdbe.org/2w50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w50 RCSB], [https://www.ebi.ac.uk/pdbsum/2w50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w50 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[https://www.uniprot.org/uniprot/CDNF_HUMAN CDNF_HUMAN]] Trophic factor for dopamine neurons. Prevents the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons. When administered after 6-OHDA-lesioning, restores the dopaminergic function and prevents the degeneration of dopaminergic neurons in substantia nigra (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w5/2w50_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2w50 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We have solved the structures of mammalian mesencephalic astrocyte-derived neurotrophic factor (MANF) and conserved dopamine neurotrophic factor (CDNF). CDNF protects and repairs midbrain dopaminergic neurons in vivo; MANF supports their survival in culture and is also cytoprotective against endoplasmic reticulum (ER) stress. Neither protein structure resembles any known growth factor but the N-terminal domain is a saposin-like lipid-binding domain. MANF and CDNF may thus bind lipids or membranes. Consistent with this, there are two patches of conserved lysines and arginines. The natively unfolded MANF C-terminus contains a CKGC disulphide bridge, such as reductases and disulphide isomerases, consistent with a role in ER stress response. The structure thus explains why MANF and CDNF are bifunctional; neurotrophic activity may reside in the N-terminal domain and ER stress response in the C-terminal domain. Finally, we identified three changes, (MANF)I10--&gt;K(CDNF), (MANF)E79--&gt;M(CDNF) and (MANF)K88--&gt;L(CDNF), that may account for the biological differences between the proteins.
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===N-TERMINAL DOMAIN OF HUMAN CONSERVED DOPAMINE NEUROTROPHIC FACTOR (CDNF)===
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The structure of the conserved neurotrophic factors MANF and CDNF explains why they are bifunctional.,Parkash V, Lindholm P, Peranen J, Kalkkinen N, Oksanen E, Saarma M, Leppanen VM, Goldman A Protein Eng Des Sel. 2009 Apr;22(4):233-41. Epub 2009 Mar 3. PMID:19258449<ref>PMID:19258449</ref>
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{{ABSTRACT_PUBMED_19258449}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 2w50" style="background-color:#fffaf0;"></div>
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[[2w50]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2W50 OCA].
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== References ==
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<references/>
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==Reference==
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__TOC__
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<ref group="xtra">PMID:019258449</ref><references group="xtra"/>
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Human]]
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[[Category: Goldman, A.]]
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[[Category: Large Structures]]
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[[Category: Kalkkinen, N.]]
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[[Category: Goldman, A]]
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[[Category: Leppanen, V M.]]
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[[Category: Kalkkinen, N]]
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[[Category: Lindholm, P.]]
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[[Category: Leppanen, V M]]
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[[Category: Oksanen, E.]]
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[[Category: Lindholm, P]]
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[[Category: Parkash, V.]]
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[[Category: Oksanen, E]]
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[[Category: Peranen, J.]]
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[[Category: Parkash, V]]
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[[Category: Saarma, M.]]
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[[Category: Peranen, J]]
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[[Category: Saarma, M]]
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[[Category: Alternative splicing]]
[[Category: Cdnf]]
[[Category: Cdnf]]
[[Category: Er stress]]
[[Category: Er stress]]

Current revision

N-terminal domain of human conserved dopamine neurotrophic factor (CDNF)

PDB ID 2w50

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