2w50: Difference between revisions
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==N-terminal domain of human conserved dopamine neurotrophic factor (CDNF)== | |||
<StructureSection load='2w50' size='340' side='right'caption='[[2w50]], [[Resolution|resolution]] 1.60Å' 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]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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-->K(CDNF), (MANF)E79-->M(CDNF) and (MANF)K88-->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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2w50" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
== | __TOC__ | ||
< | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: Goldman, A | [[Category: Large Structures]] | ||
[[Category: Kalkkinen, N | [[Category: Goldman, A]] | ||
[[Category: Leppanen, V M | [[Category: Kalkkinen, N]] | ||
[[Category: Lindholm, P | [[Category: Leppanen, V M]] | ||
[[Category: Oksanen, E | [[Category: Lindholm, P]] | ||
[[Category: Parkash, V | [[Category: Oksanen, E]] | ||
[[Category: Peranen, J | [[Category: Parkash, V]] | ||
[[Category: Saarma, M | [[Category: Peranen, J]] | ||
[[Category: Saarma, M]] | |||
[[Category: Alternative splicing]] | |||
[[Category: Cdnf]] | [[Category: Cdnf]] | ||
[[Category: Er stress]] | [[Category: Er stress]] | ||
Latest revision as of 10:52, 7 July 2021
N-terminal domain of human conserved dopamine neurotrophic factor (CDNF)
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