2w51
From Proteopedia
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| - | <StructureSection load='2w51' size='340' side='right' caption='[[2w51]], [[Resolution|resolution]] 2.80Å' scene=''> | + | ==Human mesencephalic astrocyte-derived neurotrophic factor (MANF)== |
| + | <StructureSection load='2w51' size='340' side='right'caption='[[2w51]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2w51]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2w51]] is a 1 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=2W51 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W51 FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2w51 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w51 OCA], [https://pdbe.org/2w51 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w51 RCSB], [https://www.ebi.ac.uk/pdbsum/2w51 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w51 ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/MANF_HUMAN MANF_HUMAN] Familial pancreatic carcinoma. | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/MANF_HUMAN MANF_HUMAN] Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain. Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra. Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons (By similarity). Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death.<ref>PMID:12794311</ref> <ref>PMID:18561914</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w5/2w51_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w5/2w51_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | + | </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=2w51 ConSurf]. |
<div style="clear:both"></div> | <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. | ||
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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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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Goldman | + | [[Category: Large Structures]] |
| - | [[Category: Kalkkinen | + | [[Category: Goldman A]] |
| - | [[Category: Leppanen | + | [[Category: Kalkkinen N]] |
| - | [[Category: Lindholm | + | [[Category: Leppanen VM]] |
| - | [[Category: Oksanen | + | [[Category: Lindholm P]] |
| - | [[Category: Parkash | + | [[Category: Oksanen E]] |
| - | [[Category: Peranen | + | [[Category: Parkash V]] |
| - | [[Category: Saarma | + | [[Category: Peranen J]] |
| - | + | [[Category: Saarma M]] | |
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Current revision
Human mesencephalic astrocyte-derived neurotrophic factor (MANF)
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Categories: Homo sapiens | Large Structures | Goldman A | Kalkkinen N | Leppanen VM | Lindholm P | Oksanen E | Parkash V | Peranen J | Saarma M
