9qid: Difference between revisions

Latest revision as of 15:07, 10 June 2026

Human Mortalin (mitochondrial Hsp70) in complex with wild-type GrpE1

Structural highlights

9qid is a 3 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:	Electron Microscopy, Resolution 2.73Å
Ligands:	ATP, MG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

HSPA9_HUMAN Autosomal recessive sideroblastic anemia;EVEN-plus syndrome. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

HSPA9_HUMAN Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382).[UniProtKB:P0CS90][UniProtKB:P38647]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

References

↑ Pilzer D, Fishelson Z. Mortalin/GRP75 promotes release of membrane vesicles from immune attacked cells and protection from complement-mediated lysis. Int Immunol. 2005 Sep;17(9):1239-48. PMID:16091382 doi:10.1093/intimm/dxh300
↑ Zhai P, Stanworth C, Liu S, Silberg JJ. The human escort protein Hep binds to the ATPase domain of mitochondrial hsp70 and regulates ATP hydrolysis. J Biol Chem. 2008 Sep 19;283(38):26098-106. PMID:18632665 doi:10.1074/jbc.M803475200
↑ Chen TH, Kambal A, Krysiak K, Walshauser MA, Raju G, Tibbitts JF, Walter MJ. Knockdown of Hspa9, a del(5q31.2) gene, results in a decrease in hematopoietic progenitors in mice. Blood. 2011 Feb 3;117(5):1530-9. PMID:21123823 doi:10.1182/blood-2010-06-293167
↑ Sane S, Abdullah A, Boudreau DA, Autenried RK, Gupta BK, Wang X, Wang H, Schlenker EH, Zhang D, Telleria C, Huang L, Chauhan SC, Rezvani K. Ubiquitin-like (UBX)-domain-containing protein, UBXN2A, promotes cell death by interfering with the p53-Mortalin interactions in colon cancer cells. Cell Death Dis. 2014 Mar 13;5(3):e1118. doi: 10.1038/cddis.2014.100. PMID:24625977 doi:https://dx.doi.org/10.1038/cddis.2014.100
↑ Dores-Silva PR, Barbosa LR, Ramos CH, Borges JC. Human mitochondrial Hsp70 (mortalin): shedding light on ATPase activity, interaction with adenosine nucleotides, solution structure and domain organization. PLoS One. 2015 Jan 23;10(1):e0117170. doi: 10.1371/journal.pone.0117170. , eCollection 2015. PMID:25615450 doi:https://dx.doi.org/10.1371/journal.pone.0117170
↑ Sane S, Abdullah A, Nelson ME, Wang H, Chauhan SC, Newton SS, Rezvani K. Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy. Cell Stress Chaperones. 2016 Mar;21(2):313-26. doi: 10.1007/s12192-015-0661-5. , Epub 2015 Dec 4. PMID:26634371 doi:https://dx.doi.org/10.1007/s12192-015-0661-5
↑ Shan Y, Cortopassi G. Mitochondrial Hspa9/Mortalin regulates erythroid differentiation via iron-sulfur cluster assembly. Mitochondrion. 2016 Jan;26:94-103. doi: 10.1016/j.mito.2015.12.005. Epub 2015 Dec , 17. PMID:26702583 doi:https://dx.doi.org/10.1016/j.mito.2015.12.005
↑ Srivastava S, Savanur MA, Sinha D, Birje A, R V, Saha PP, D'Silva P. Regulation of mitochondrial protein import by the nucleotide exchange factors GrpEL1 and GrpEL2 in human cells. J Biol Chem. 2017 Nov 3;292(44):18075-18090. doi: 10.1074/jbc.M117.788463. Epub , 2017 Aug 28. PMID:28848044 doi:https://dx.doi.org/10.1074/jbc.M117.788463
↑ Moseng MA, Nix JC, Page RC. Biophysical Consequences of EVEN-PLUS Syndrome Mutations for the Function of Mortalin. J Phys Chem B. 2019 Apr 12. doi: 10.1021/acs.jpcb.9b00071. PMID:30933555 doi:https://dx.doi.org/10.1021/acs.jpcb.9b00071
↑ Moseng MA, Nix JC, Page RC. 2- and N6-Functionalized Adenosine-5'-diphosphate Analogues for the Inhibition of Mortalin. FEBS Lett. 2019 Jun 8. doi: 10.1002/1873-3468.13475. PMID:31177526 doi:https://dx.doi.org/10.1002/1873-3468.13475

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Pilzer D, Fishelson Z. Mortalin/GRP75 promotes release of membrane vesicles from immune attacked cells and protection from complement-mediated lysis. Int Immunol. 2005 Sep;17(9):1239-48. PMID:16091382 doi:10.1093/intimm/dxh300

[2] Zhai P, Stanworth C, Liu S, Silberg JJ. The human escort protein Hep binds to the ATPase domain of mitochondrial hsp70 and regulates ATP hydrolysis. J Biol Chem. 2008 Sep 19;283(38):26098-106. PMID:18632665 doi:10.1074/jbc.M803475200

[3] Chen TH, Kambal A, Krysiak K, Walshauser MA, Raju G, Tibbitts JF, Walter MJ. Knockdown of Hspa9, a del(5q31.2) gene, results in a decrease in hematopoietic progenitors in mice. Blood. 2011 Feb 3;117(5):1530-9. PMID:21123823 doi:10.1182/blood-2010-06-293167

[4] Sane S, Abdullah A, Boudreau DA, Autenried RK, Gupta BK, Wang X, Wang H, Schlenker EH, Zhang D, Telleria C, Huang L, Chauhan SC, Rezvani K. Ubiquitin-like (UBX)-domain-containing protein, UBXN2A, promotes cell death by interfering with the p53-Mortalin interactions in colon cancer cells. Cell Death Dis. 2014 Mar 13;5(3):e1118. doi: 10.1038/cddis.2014.100. PMID:24625977 doi:https://dx.doi.org/10.1038/cddis.2014.100

[5] Dores-Silva PR, Barbosa LR, Ramos CH, Borges JC. Human mitochondrial Hsp70 (mortalin): shedding light on ATPase activity, interaction with adenosine nucleotides, solution structure and domain organization. PLoS One. 2015 Jan 23;10(1):e0117170. doi: 10.1371/journal.pone.0117170. , eCollection 2015. PMID:25615450 doi:https://dx.doi.org/10.1371/journal.pone.0117170

[6] Sane S, Abdullah A, Nelson ME, Wang H, Chauhan SC, Newton SS, Rezvani K. Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy. Cell Stress Chaperones. 2016 Mar;21(2):313-26. doi: 10.1007/s12192-015-0661-5. , Epub 2015 Dec 4. PMID:26634371 doi:https://dx.doi.org/10.1007/s12192-015-0661-5

[7] Shan Y, Cortopassi G. Mitochondrial Hspa9/Mortalin regulates erythroid differentiation via iron-sulfur cluster assembly. Mitochondrion. 2016 Jan;26:94-103. doi: 10.1016/j.mito.2015.12.005. Epub 2015 Dec , 17. PMID:26702583 doi:https://dx.doi.org/10.1016/j.mito.2015.12.005

[8] Srivastava S, Savanur MA, Sinha D, Birje A, R V, Saha PP, D'Silva P. Regulation of mitochondrial protein import by the nucleotide exchange factors GrpEL1 and GrpEL2 in human cells. J Biol Chem. 2017 Nov 3;292(44):18075-18090. doi: 10.1074/jbc.M117.788463. Epub , 2017 Aug 28. PMID:28848044 doi:https://dx.doi.org/10.1074/jbc.M117.788463

[9] Moseng MA, Nix JC, Page RC. Biophysical Consequences of EVEN-PLUS Syndrome Mutations for the Function of Mortalin. J Phys Chem B. 2019 Apr 12. doi: 10.1021/acs.jpcb.9b00071. PMID:30933555 doi:https://dx.doi.org/10.1021/acs.jpcb.9b00071

[10] Moseng MA, Nix JC, Page RC. 2- and N6-Functionalized Adenosine-5'-diphosphate Analogues for the Inhibition of Mortalin. FEBS Lett. 2019 Jun 8. doi: 10.1002/1873-3468.13475. PMID:31177526 doi:https://dx.doi.org/10.1002/1873-3468.13475

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9qid is ON HOLD
+==Human Mortalin (mitochondrial Hsp70) in complex with wild-type GrpE1==
+<StructureSection load='9qid' size='340' side='right'caption='[[9qid]], [[Resolution|resolution]] 2.73&Aring;' scene=''>
-Authors: Bauer, J.A., Pinkas, M.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9qid]] is a 3 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=9QID OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QID FirstGlance]. <br>
-Description: Human Mortalin (mitochondrial Hsp70) in complex with wild-type GrpE1
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.73&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-[[Category: Bauer, J.A]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9qid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qid OCA], [https://pdbe.org/9qid PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qid RCSB], [https://www.ebi.ac.uk/pdbsum/9qid PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qid ProSAT]</span></td></tr>
-[[Category: Pinkas, M]]
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/HSPA9_HUMAN HSPA9_HUMAN] Autosomal recessive sideroblastic anemia;EVEN-plus syndrome. The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/HSPA9_HUMAN HSPA9_HUMAN] Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382).[UniProtKB:P0CS90][UniProtKB:P38647]<ref>PMID:16091382</ref> <ref>PMID:18632665</ref> <ref>PMID:21123823</ref> <ref>PMID:24625977</ref> <ref>PMID:25615450</ref> <ref>PMID:26634371</ref> <ref>PMID:26702583</ref> <ref>PMID:28848044</ref> <ref>PMID:30933555</ref> <ref>PMID:31177526</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bauer JA]]
+[[Category: Pinkas M]]

9qid: Difference between revisions

Latest revision as of 15:07, 10 June 2026

Human Mortalin (mitochondrial Hsp70) in complex with wild-type GrpE1

Structural highlights

Disease

Function

References

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