View source for 2w50


==N-terminal domain of human conserved dopamine neurotrophic factor (CDNF)==
<StructureSection load='2w50' size='340' side='right'caption='[[2w50]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<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>
</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>
<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>
</table>
== Function ==
[[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). 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w5/2w50_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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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== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2w50" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Goldman, A]]
[[Category: Kalkkinen, N]]
[[Category: Leppanen, V M]]
[[Category: Lindholm, P]]
[[Category: Oksanen, E]]
[[Category: Parkash, V]]
[[Category: Peranen, J]]
[[Category: Saarma, M]]
[[Category: Alternative splicing]]
[[Category: Cdnf]]
[[Category: Er stress]]
[[Category: Growth factor]]
[[Category: Hormone]]
[[Category: Manf]]
[[Category: Neurotrophic factor]]
[[Category: Saposin]]
[[Category: Secreted]]