8i6v
Cryo-EM structure of the polyphosphate polymerase VTC complex(Vtc4/Vtc3/Vtc1)
Structural highlights
FunctionVTC1_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 PubMedThe 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
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