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TitleThe cytoplasmic synthesis and coupled membrane translocation of eukaryotic polyphosphate by signal-activated VTC complex.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 718, Year 2023
Publish dateFeb 9, 2023
AuthorsZeyuan Guan / Juan Chen / Ruiwen Liu / Yanke Chen / Qiong Xing / Zhangmeng Du / Meng Cheng / Jianjian Hu / Wenhui Zhang / Wencong Mei / Beijing Wan / Qiang Wang / Jie Zhang / Peng Cheng / Huanyu Cai / Jianbo Cao / Delin Zhang / Junjie Yan / Ping Yin / Michael Hothorn / Zhu Liu /
PubMed AbstractInorganic polyphosphate (polyP) is an ancient energy metabolite and phosphate store that occurs ubiquitously in all organisms. The vacuolar transporter chaperone (VTC) complex integrates cytosolic ...Inorganic polyphosphate (polyP) is an ancient energy metabolite and phosphate store that occurs ubiquitously in all organisms. The vacuolar transporter chaperone (VTC) complex integrates cytosolic polyP synthesis from ATP and polyP membrane translocation into the vacuolar lumen. In yeast and in other eukaryotes, polyP synthesis is regulated by inositol pyrophosphate (PP-InsP) nutrient messengers, directly sensed by the VTC complex. Here, we report the cryo-electron microscopy structure of signal-activated VTC complex at 3.0 Å resolution. Baker's yeast VTC subunits Vtc1, Vtc3, and Vtc4 assemble into a 3:1:1 complex. Fifteen trans-membrane helices form a novel membrane channel enabling the transport of newly synthesized polyP into the vacuolar lumen. PP-InsP binding orients the catalytic polymerase domain at the entrance of the trans-membrane channel, both activating the enzyme and coupling polyP synthesis and membrane translocation. Together with biochemical and cellular studies, our work provides mechanistic insights into the biogenesis of an ancient energy metabolite.
External linksNat Commun / PubMed:36759618 / PubMed Central
MethodsEM (single particle)
Resolution3.0 Å
Structure data

34090

7ytj

EMDB-34090, PDB-7ytj:
Cryo-EM structure of VTC complex
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE / Phytic acid

ChemComp-PC1:
1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM / Phosphatidylcholine

ChemComp-PO4:
PHOSPHATE ION / Phosphate

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsTRANSPORT PROTEIN / VTC complex / Poly P.

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