8i6v

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of the polyphosphate polymerase VTC complex(Vtc4/Vtc3/Vtc1)

Structural highlights

8i6v is a 5 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.06Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VTC1_YEAST Accessory subunit of the vacuolar transporter chaperone (VTC) complex. The VTC complex acts as a vacuolar polyphosphate polymerase that catalyzes the synthesis of inorganic polyphosphate (polyP) via transfer of phosphate from ATP to a growing polyP chain, releasing ADP. VTC exposes its catalytic domain VTC4 to the cytosol, where the growing polyP chain winds through a tunnel-shaped pocket, integrating cytoplasmic polymer synthesis with polyP membrane translocation (PubMed:19390046). The VTC complex carries 9 vacuolar transmembrane domains, which are likely to constitute the translocation channel into the organelle lumen (PubMed:19390046, PubMed:25315834). PolyP synthesis is tightly coupled to its transport into the vacuole lumen, in order to avoid otherwise toxic intermediates in the cytosol, and it depends on the proton gradient across the membrane, formed by V-ATPase (PubMed:25315834). VTC1 contributes only 3 transmembrane domains to the complex (Probable). The VTC complex also plays a role in vacuolar membrane fusion (PubMed:10480897, PubMed:11102525, PubMed:11823419, PubMed:12584253). Required for SEC18/NSF activity in SNARE priming, membrane binding of LMA1 and V(0) trans-complex formation (PubMed:11823419).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

The eukaryotic vacuolar transporter chaperone (VTC) complex acts as a polyphosphate (polyP) polymerase that synthesizes polyP from adenosine triphosphate (ATP) and translocates polyP across the vacuolar membrane to maintain an intracellular phosphate (P(i) ) homeostasis. To discover how the VTC complex performs its function, we determined a cryo-electron microscopy structure of an endogenous VTC complex (Vtc4/Vtc3/Vtc1) purified from Saccharomyces cerevisiae at 3.1 A resolution. The structure reveals a heteropentameric architecture of one Vtc4, one Vtc3, and three Vtc1 subunits. The transmembrane region forms a polyP-selective channel, likely adopting a resting state conformation, in which a latch-like, horizontal helix of Vtc4 limits the entrance. The catalytic Vtc4 central domain is located on top of the pseudo-symmetric polyP channel, creating a strongly electropositive pathway for nascent polyP that can couple synthesis to translocation. The SPX domain of the catalytic Vtc4 subunit positively regulates polyP synthesis by the VTC complex. The noncatalytic Vtc3 regulates VTC through a phosphorylatable loop. Our findings, along with the functional data, allow us to propose a mechanism of polyP channel gating and VTC complex activation.

Cryo-EM structure of the polyphosphate polymerase VTC reveals coupling of polymer synthesis to membrane transit.,Liu W, Wang J, Comte-Miserez V, Zhang M, Yu X, Chen Q, Jessen HJ, Mayer A, Wu S, Ye S EMBO J. 2023 May 15;42(10):e113320. doi: 10.15252/embj.2022113320. Epub 2023 Apr , 17. PMID:37066886^[8]

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

References

↑ Cohen A, Perzov N, Nelson H, Nelson N. A novel family of yeast chaperons involved in the distribution of V-ATPase and other membrane proteins. J Biol Chem. 1999 Sep 17;274(38):26885-93. PMID:10480897 doi:10.1074/jbc.274.38.26885
↑ Ogawa N, DeRisi J, Brown PO. New components of a system for phosphate accumulation and polyphosphate metabolism in Saccharomyces cerevisiae revealed by genomic expression analysis. Mol Biol Cell. 2000 Dec;11(12):4309-21. PMID:11102525
↑ Muller O, Bayer MJ, Peters C, Andersen JS, Mann M, Mayer A. The Vtc proteins in vacuole fusion: coupling NSF activity to V(0) trans-complex formation. EMBO J. 2002 Feb 1;21(3):259-69. PMID:11823419 doi:http://dx.doi.org/10.1093/emboj/21.3.259
↑ Muller O, Neumann H, Bayer MJ, Mayer A. Role of the Vtc proteins in V-ATPase stability and membrane trafficking. J Cell Sci. 2003 Mar 15;116(Pt 6):1107-15. PMID:12584253
↑ Hothorn M, Neumann H, Lenherr ED, Wehner M, Rybin V, Hassa PO, Uttenweiler A, Reinhardt M, Schmidt A, Seiler J, Ladurner AG, Herrmann C, Scheffzek K, Mayer A. Catalytic core of a membrane-associated eukaryotic polyphosphate polymerase. Science. 2009 Apr 24;324(5926):513-6. PMID:19390046 doi:324/5926/513
↑ Gerasimaitė R, Sharma S, Desfougères Y, Schmidt A, Mayer A. Coupled synthesis and translocation restrains polyphosphate to acidocalcisome-like vacuoles and prevents its toxicity. J Cell Sci. 2014 Dec 1;127(Pt 23):5093-104. PMID:25315834 doi:10.1242/jcs.159772
↑ Hothorn M, Neumann H, Lenherr ED, Wehner M, Rybin V, Hassa PO, Uttenweiler A, Reinhardt M, Schmidt A, Seiler J, Ladurner AG, Herrmann C, Scheffzek K, Mayer A. Catalytic core of a membrane-associated eukaryotic polyphosphate polymerase. Science. 2009 Apr 24;324(5926):513-6. PMID:19390046 doi:324/5926/513
↑ Liu W, Wang J, Comte-Miserez V, Zhang M, Yu X, Chen Q, Jessen HJ, Mayer A, Wu S, Ye S. Cryo-EM structure of the polyphosphate polymerase VTC reveals coupling of polymer synthesis to membrane transit. EMBO J. 2023 May 15;42(10):e113320. PMID:37066886 doi:10.15252/embj.2022113320

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8i6v"

Categories: Large Structures | Saccharomyces cerevisiae S288C | Mayer A | Wu S | Ye S

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8i6v]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8I6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8I6V FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PO:TRIPHOSPHATE'>3PO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.06&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PO:TRIPHOSPHATE'>3PO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</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=8i6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8i6v OCA], [https://pdbe.org/8i6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8i6v RCSB], [https://www.ebi.ac.uk/pdbsum/8i6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8i6v ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/VTC4_YEAST VTC4_YEAST] Component of the vacuolar transporter chaperone (VTC) complex, which plays a role in vacuolar membrane fusion. Required for SEC18/NSF activity in SNARE priming, membrane binding of LMA1 and V(0) trans-complex formation.<ref>PMID:11102525</ref> <ref>PMID:11823419</ref> <ref>PMID:12584253</ref>
+[https://www.uniprot.org/uniprot/VTC1_YEAST VTC1_YEAST] Accessory subunit of the vacuolar transporter chaperone (VTC) complex. The VTC complex acts as a vacuolar polyphosphate polymerase that catalyzes the synthesis of inorganic polyphosphate (polyP) via transfer of phosphate from ATP to a growing polyP chain, releasing ADP. VTC exposes its catalytic domain VTC4 to the cytosol, where the growing polyP chain winds through a tunnel-shaped pocket, integrating cytoplasmic polymer synthesis with polyP membrane translocation (PubMed:19390046). The VTC complex carries 9 vacuolar transmembrane domains, which are likely to constitute the translocation channel into the organelle lumen (PubMed:19390046, PubMed:25315834). PolyP synthesis is tightly coupled to its transport into the vacuole lumen, in order to avoid otherwise toxic intermediates in the cytosol, and it depends on the proton gradient across the membrane, formed by V-ATPase (PubMed:25315834). VTC1 contributes only 3 transmembrane domains to the complex (Probable). The VTC complex also plays a role in vacuolar membrane fusion (PubMed:10480897, PubMed:11102525, PubMed:11823419, PubMed:12584253). Required for SEC18/NSF activity in SNARE priming, membrane binding of LMA1 and V(0) trans-complex formation (PubMed:11823419).<ref>PMID:10480897</ref> <ref>PMID:11102525</ref> <ref>PMID:11823419</ref> <ref>PMID:12584253</ref> <ref>PMID:19390046</ref> <ref>PMID:25315834</ref> <ref>PMID:19390046</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The eukaryotic vacuolar transporter chaperone (VTC) complex acts as a polyphosphate (polyP) polymerase that synthesizes polyP from adenosine triphosphate (ATP) and translocates polyP across the vacuolar membrane to maintain an intracellular phosphate (P(i) ) homeostasis. To discover how the VTC complex performs its function, we determined a cryo-electron microscopy structure of an endogenous VTC complex (Vtc4/Vtc3/Vtc1) purified from Saccharomyces cerevisiae at 3.1 A resolution. The structure reveals a heteropentameric architecture of one Vtc4, one Vtc3, and three Vtc1 subunits. The transmembrane region forms a polyP-selective channel, likely adopting a resting state conformation, in which a latch-like, horizontal helix of Vtc4 limits the entrance. The catalytic Vtc4 central domain is located on top of the pseudo-symmetric polyP channel, creating a strongly electropositive pathway for nascent polyP that can couple synthesis to translocation. The SPX domain of the catalytic Vtc4 subunit positively regulates polyP synthesis by the VTC complex. The noncatalytic Vtc3 regulates VTC through a phosphorylatable loop. Our findings, along with the functional data, allow us to propose a mechanism of polyP channel gating and VTC complex activation.
+Cryo-EM structure of the polyphosphate polymerase VTC reveals coupling of polymer synthesis to membrane transit.,Liu W, Wang J, Comte-Miserez V, Zhang M, Yu X, Chen Q, Jessen HJ, Mayer A, Wu S, Ye S EMBO J. 2023 May 15;42(10):e113320. doi: 10.15252/embj.2022113320. Epub 2023 Apr , 17. PMID:37066886<ref>PMID:37066886</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 8i6v" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

8i6v

From Proteopedia

Current revision

Cryo-EM structure of the polyphosphate polymerase VTC complex(Vtc4/Vtc3/Vtc1)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox