| Structural highlights
Function
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.[1] [2] [3]
Publication Abstract from PubMed
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 A 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.
The cytoplasmic synthesis and coupled membrane translocation of eukaryotic polyphosphate by signal-activated VTC complex.,Guan Z, Chen J, Liu R, Chen Y, Xing Q, Du Z, Cheng M, Hu J, Zhang W, Mei W, Wan B, Wang Q, Zhang J, Cheng P, Cai H, Cao J, Zhang D, Yan J, Yin P, Hothorn M, Liu Z Nat Commun. 2023 Feb 9;14(1):718. doi: 10.1038/s41467-023-36466-4. PMID:36759618[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ Guan Z, Chen J, Liu R, Chen Y, Xing Q, Du Z, Cheng M, Hu J, Zhang W, Mei W, Wan B, Wang Q, Zhang J, Cheng P, Cai H, Cao J, Zhang D, Yan J, Yin P, Hothorn M, Liu Z. The cytoplasmic synthesis and coupled membrane translocation of eukaryotic polyphosphate by signal-activated VTC complex. Nat Commun. 2023 Feb 9;14(1):718. PMID:36759618 doi:10.1038/s41467-023-36466-4
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