8I6V

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

Summary for 8I6V

• Entry DOI: 10.2210/pdb8i6v/pdb
• EMDB information: 35208
• Descriptor: Vacuolar transporter chaperone complex subunit 1, Vacuolar transporter chaperone 3 complex subunit 3, Vacuolar transporter chaperone complex subunit 4, ... (8 entities in total)
• Functional Keywords: polyphosphate polymerase; vtc complex; coupled synthesis and translocation, membrane protein
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 5
• Total formula weight: 224475.02

Authors

Mayer, A.,Wu, S.,Ye, S. (deposition date: 2023-01-29, release date: 2023-03-01, Last modification date: 2025-07-16)

Primary citation

Liu, W.,Wang, J.,Comte-Miserez, V.,Zhang, M.,Yu, X.,Chen, Q.,Jessen, H.J.,Mayer, A.,Wu, S.,Ye, S.
Cryo-EM structure of the polyphosphate polymerase VTC reveals coupling of polymer synthesis to membrane transit.
Embo J., 42:e113320-e113320, 2023

PubMed Abstract: 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 ) 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 Å 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.

PubMed: 37066886
DOI: 10.15252/embj.2022113320

Experimental method

ELECTRON MICROSCOPY (3.06 Å)