7n1r

From Proteopedia

(Difference between revisions)

Current revision

A novel and unique ATP hydrolysis to AMP by a human Hsp70 BiP

Structural highlights

7n1r is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.03Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

Hsp70s are ubiquitous and highly conserved molecular chaperones. They play crucial roles in maintaining cellular protein homeostasis. It is well established that Hsp70s use the energy of ATP hydrolysis to ADP to power the chaperone activity regardless of the cellular locations and isoforms. Binding immunoglobin protein (BiP), the major member of Hsp70s in the endoplasmic reticulum, is essential for protein folding and quality control. Unexpectedly, our structural analysis of BiP demonstrated a novel ATP hydrolysis to AMP during crystallization under the acidic conditions. Our biochemical studies confirmed this newly discovered ATP to AMP hydrolysis in solutions. Unlike the canonical ATP to ADP hydrolysis observed for Hsp70s, this ATP hydrolysis to AMP depends on the substrate-binding domain of BiP and is inhibited by the binding of a peptide substrate. Intriguingly, this ATP to AMP hydrolysis is unique to BiP, not shared by two representative Hsp70 proteins from the cytosol. Taken together, this novel and unique ATP to AMP hydrolysis may provide a potentially new direction for understanding the activity and cellular function of BiP.

A novel and unique ATP hydrolysis to AMP by a human Hsp70 Binding immunoglobin protein (BiP).,Li H, Musayev FN, Yang J, Su J, Liu Q, Wang W, Fang X, Zhou L, Liu Q Protein Sci. 2021 Dec 23. doi: 10.1002/pro.4267. PMID:34941000^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Li H, Musayev FN, Yang J, Su J, Liu Q, Wang W, Fang X, Zhou L, Liu Q. A novel and unique ATP hydrolysis to AMP by a human Hsp70 Binding immunoglobin protein (BiP). Protein Sci. 2021 Dec 23. doi: 10.1002/pro.4267. PMID:34941000 doi:http://dx.doi.org/10.1002/pro.4267

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7n1r"

Categories: Homo sapiens | Large Structures | Liu Q | Musayev F | Yang J

@@ Line 3: / Line 3: @@
 <StructureSection load='7n1r' size='340' side='right'caption='[[7n1r]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7n1r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N1R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N1R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7n1r]] 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=7N1R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N1R FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.03&#8491;</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=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7n1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n1r OCA], [https://pdbe.org/7n1r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n1r RCSB], [https://www.ebi.ac.uk/pdbsum/7n1r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n1r ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/BIP_HUMAN BIP_HUMAN]] 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 ==
-[[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>
+[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 ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Non-chaperonin molecular chaperone ATPase]]
+[[Category: Liu Q]]
-[[Category: Liu, Q]]
+[[Category: Musayev F]]
-[[Category: Musayev, F]]
+[[Category: Yang J]]
-[[Category: Yang, J]]
-[[Category: Chaperone]]
-[[Category: Protein-ligand complex]]

7n1r

From Proteopedia

Current revision

A novel and unique ATP hydrolysis to AMP by a human Hsp70 BiP

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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