|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6ha7' size='340' side='right'caption='[[6ha7]], [[Resolution|resolution]] 2.49Å' scene=''> | | <StructureSection load='6ha7' size='340' side='right'caption='[[6ha7]], [[Resolution|resolution]] 2.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ha7]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HA7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HA7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ha7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetulus_griseus Cricetulus griseus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HA7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HA7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 2.49Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-chaperonin_molecular_chaperone_ATPase Non-chaperonin molecular chaperone ATPase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.10 3.6.4.10] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6ha7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ha7 OCA], [https://pdbe.org/6ha7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ha7 RCSB], [https://www.ebi.ac.uk/pdbsum/6ha7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ha7 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=6ha7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ha7 OCA], [https://pdbe.org/6ha7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ha7 RCSB], [https://www.ebi.ac.uk/pdbsum/6ha7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ha7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/BIP_CRIGR BIP_CRIGR]] Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (By similarity). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:29198525). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (PubMed:29198525). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (PubMed:29198525). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating.[UniProtKB:P11021][UniProtKB:P20029]<ref>PMID:29198525</ref> [[https://www.uniprot.org/uniprot/MANF_MOUSE MANF_MOUSE]] 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. Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death. Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions. Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia. Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells. Sulfatide binding promotes its cellular uptake by endocytosis, and is required for its role in alleviating ER stress and cell toxicity under hypoxic and ER stress conditions.[UniProtKB:P0C5H9][UniProtKB:P55145]
| + | [https://www.uniprot.org/uniprot/BIP_CRIGR BIP_CRIGR] Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (By similarity). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:29198525). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (PubMed:29198525). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (PubMed:29198525). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating.[UniProtKB:P11021][UniProtKB:P20029]<ref>PMID:29198525</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 26: |
Line 26: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Cricetulus griseus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-chaperonin molecular chaperone ATPase]] | + | [[Category: Mus musculus]] |
| - | [[Category: Ron, D]] | + | [[Category: Ron D]] |
| - | [[Category: Yan, Y]] | + | [[Category: Yan Y]] |
| - | [[Category: Armet]]
| + | |
| - | [[Category: Bip]]
| + | |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Hsp70]]
| + | |
| - | [[Category: Manf]]
| + | |
| - | [[Category: Nbd]]
| + | |
| - | [[Category: Ndi]]
| + | |
| Structural highlights
Function
BIP_CRIGR Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (By similarity). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:29198525). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (PubMed:29198525). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (PubMed:29198525). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating.[UniProtKB:P11021][UniProtKB:P20029][1]
Publication Abstract from PubMed
Despite its known role as a secreted neuroprotectant, much of the mesencephalic astrocyte-derived neurotrophic factor (MANF) is retained in the endoplasmic reticulum (ER) of producer cells. There, by unknown mechanisms, MANF plays a role in protein folding homeostasis in complex with the ER-localized Hsp70 chaperone BiP. Here we report that the SAF-A/B, Acinus, and PIAS (SAP) domain of MANF selectively associates with the nucleotide binding domain (NBD) of ADP-bound BiP. In crystal structures the SAP domain engages the cleft between NBD subdomains Ia and IIa, stabilizing the ADP-bound conformation and clashing with the interdomain linker that occupies this site in ATP-bound BiP. MANF inhibits both ADP release from BiP and ATP binding to BiP, and thereby client release. Cells lacking MANF have fewer ER stress-induced BiP-containing high molecular weight complexes. These findings suggest that MANF contributes to protein folding homeostasis as a nucleotide exchange inhibitor that stabilizes certain BiP-client complexes.
MANF antagonizes nucleotide exchange by the endoplasmic reticulum chaperone BiP.,Yan Y, Rato C, Rohland L, Preissler S, Ron D Nat Commun. 2019 Feb 1;10(1):541. doi: 10.1038/s41467-019-08450-4. PMID:30710085[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Amin-Wetzel N, Saunders RA, Kamphuis MJ, Rato C, Preissler S, Harding HP, Ron D. A J-Protein Co-chaperone Recruits BiP to Monomerize IRE1 and Repress the Unfolded Protein Response. Cell. 2017 Dec 14;171(7):1625-1637.e13. doi: 10.1016/j.cell.2017.10.040. Epub, 2017 Nov 30. PMID:29198525 doi:http://dx.doi.org/10.1016/j.cell.2017.10.040
- ↑ Yan Y, Rato C, Rohland L, Preissler S, Ron D. MANF antagonizes nucleotide exchange by the endoplasmic reticulum chaperone BiP. Nat Commun. 2019 Feb 1;10(1):541. doi: 10.1038/s41467-019-08450-4. PMID:30710085 doi:http://dx.doi.org/10.1038/s41467-019-08450-4
|
