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| | <StructureSection load='3ldp' size='340' side='right'caption='[[3ldp]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='3ldp' size='340' side='right'caption='[[3ldp]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ldp]] 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=3LDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LDP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ldp]] is a 2 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=3LDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LDP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3P1:8-[(QUINOLIN-2-YLMETHYL)AMINO]ADENOSINE'>3P1</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ldl|3ldl]], [[3ldn|3ldn]], [[3ldo|3ldo]], [[3ldq|3ldq]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3P1:8-[(QUINOLIN-2-YLMETHYL)AMINO]ADENOSINE'>3P1</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSPA5, GRP78 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3ldp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ldp OCA], [https://pdbe.org/3ldp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ldp RCSB], [https://www.ebi.ac.uk/pdbsum/3ldp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ldp 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=3ldp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ldp OCA], [https://pdbe.org/3ldp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ldp RCSB], [https://www.ebi.ac.uk/pdbsum/3ldp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ldp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/GRP78_HUMAN GRP78_HUMAN]] Note=Autoantigen in rheumatoid arthritis.<ref>PMID:11160188</ref>
| + | [https://www.uniprot.org/uniprot/BIP_HUMAN BIP_HUMAN] Autoantigen in rheumatoid arthritis.<ref>PMID:11160188</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GRP78_HUMAN GRP78_HUMAN]] Probably plays a role in facilitating the assembly of multimeric protein complexes inside the ER.<ref>PMID:2294010</ref>
| + | [https://www.uniprot.org/uniprot/BIP_HUMAN BIP_HUMAN] Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). 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:1550958, PubMed:19538957). 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 (By similarity). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). 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:G3I8R9][UniProtKB:P20029]<ref>PMID:1550958</ref> <ref>PMID:19538957</ref> <ref>PMID:2294010</ref> <ref>PMID:23769672</ref> <ref>PMID:23990668</ref> <ref>PMID:28332555</ref> <ref>PMID:29719251</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | 78 kDa glucose-regulated protein (Grp78) is a heat shock protein (HSP) involved in protein folding that plays a role in cancer cell proliferation. Binding of adenosine-derived inhibitors to Grp78 was characterized by surface plasmon resonance and isothermal titration calorimetry. The most potent compounds were 13 (VER-155008) with K(D) = 80 nM and 14 with K(D) = 60 nM. X-ray crystal structures of Grp78 bound to ATP, ADPnP, and adenosine derivative 10 revealed differences in the binding site between Grp78 and homologous proteins.
| + | |
| - | | + | |
| - | Adenosine-Derived Inhibitors of 78 kDa Glucose Regulated Protein (Grp78) ATPase: Insights into Isoform Selectivity.,Macias AT, Williamson DS, Allen N, Borgognoni J, Clay A, Daniels Z, Dokurno P, Drysdale MJ, Francis GL, Graham CJ, Howes R, Matassova N, Murray JB, Parsons R, Shaw T, Surgenor AE, Terry L, Wang Y, Wood M, Massey AJ J Med Chem. 2011 May 20. PMID:21526763<ref>PMID:21526763</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| - | <div class="pdbe-citations 3ldp" style="background-color:#fffaf0;"></div> | + | |
| | | | |
| | ==See Also== | | ==See Also== |
| Line 29: |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dokurno, P]] | + | [[Category: Dokurno P]] |
| - | [[Category: Macias, A T]] | + | [[Category: Macias AT]] |
| - | [[Category: Massey, A J]] | + | [[Category: Massey AJ]] |
| - | [[Category: Shaw, T]] | + | [[Category: Shaw T]] |
| - | [[Category: Surgenor, A E]] | + | [[Category: Surgenor AE]] |
| - | [[Category: Williamson, D S]] | + | [[Category: Williamson DS]] |
| - | [[Category: Adenosine]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Endoplasmic reticulum]]
| + | |
| - | [[Category: Grp78]]
| + | |
| - | [[Category: Heat shock]]
| + | |
| - | [[Category: Hsc70]]
| + | |
| - | [[Category: Hsp70]]
| + | |
| - | [[Category: Nucleoside]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein folding]]
| + | |
| - | [[Category: Selectivity]]
| + | |
| - | [[Category: Small molecule inhibitor]]
| + | |
| - | [[Category: Stress response]]
| + | |
| Structural highlights
Disease
BIP_HUMAN Autoantigen in rheumatoid arthritis.[1]
Function
BIP_HUMAN Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). 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:1550958, PubMed:19538957). 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 (By similarity). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). 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:G3I8R9][UniProtKB:P20029][2] [3] [4] [5] [6] [7] [8]
See Also
References
- ↑ Corrigall VM, Bodman-Smith MD, Fife MS, Canas B, Myers LK, Wooley P, Soh C, Staines NA, Pappin DJ, Berlo SE, van Eden W, van Der Zee R, Lanchbury JS, Panayi GS. The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis. J Immunol. 2001 Feb 1;166(3):1492-8. PMID:11160188
- ↑ Ng DT, Watowich SS, Lamb RA. Analysis in vivo of GRP78-BiP/substrate interactions and their role in induction of the GRP78-BiP gene. Mol Biol Cell. 1992 Feb;3(2):143-55. doi: 10.1091/mbc.3.2.143. PMID:1550958 doi:http://dx.doi.org/10.1091/mbc.3.2.143
- ↑ Oikawa D, Kimata Y, Kohno K, Iwawaki T. Activation of mammalian IRE1alpha upon ER stress depends on dissociation of BiP rather than on direct interaction with unfolded proteins. Exp Cell Res. 2009 Sep 10;315(15):2496-504. doi: 10.1016/j.yexcr.2009.06.009., Epub 2009 Jun 16. PMID:19538957 doi:http://dx.doi.org/10.1016/j.yexcr.2009.06.009
- ↑ Dana RC, Welch WJ, Deftos LJ. Heat shock proteins bind calcitonin. Endocrinology. 1990 Jan;126(1):672-4. PMID:2294010
- ↑ Oka OB, Pringle MA, Schopp IM, Braakman I, Bulleid NJ. ERdj5 is the ER reductase that catalyzes the removal of non-native disulfides and correct folding of the LDL receptor. Mol Cell. 2013 Jun 27;50(6):793-804. doi: 10.1016/j.molcel.2013.05.014. Epub 2013, Jun 13. PMID:23769672 doi:http://dx.doi.org/10.1016/j.molcel.2013.05.014
- ↑ Evensen NA, Kuscu C, Nguyen HL, Zarrabi K, Dufour A, Kadam P, Hu YJ, Pulkoski-Gross A, Bahou WF, Zucker S, Cao J. Unraveling the role of KIAA1199, a novel endoplasmic reticulum protein, in cancer cell migration. J Natl Cancer Inst. 2013 Sep 18;105(18):1402-16. doi: 10.1093/jnci/djt224. Epub, 2013 Aug 29. PMID:23990668 doi:http://dx.doi.org/10.1093/jnci/djt224
- ↑ Cuevas EP, Eraso P, Mazon MJ, Santos V, Moreno-Bueno G, Cano A, Portillo F. LOXL2 drives epithelial-mesenchymal transition via activation of IRE1-XBP1 signalling pathway. Sci Rep. 2017 Mar 23;7:44988. doi: 10.1038/srep44988. PMID:28332555 doi:http://dx.doi.org/10.1038/srep44988
- ↑ Hassdenteufel S, Johnson N, Paton AW, Paton JC, High S, Zimmermann R. Chaperone-Mediated Sec61 Channel Gating during ER Import of Small Precursor Proteins Overcomes Sec61 Inhibitor-Reinforced Energy Barrier. Cell Rep. 2018 May 1;23(5):1373-1386. doi: 10.1016/j.celrep.2018.03.122. PMID:29719251 doi:http://dx.doi.org/10.1016/j.celrep.2018.03.122
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