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Literature summary for 3.6.4.6 extracted from

  • Han, H.; Monroe, N.; Votteler, J.; Shakya, B.; Sundquist, W.I.; Hill, C.P.
    Binding of substrates to the central pore of the Vps4 ATPase is autoinhibited by the microtubule interacting and trafficking (MIT) domain and activated by MIT interacting motifs (MIMs) (2015), J. Biol. Chem., 290, 13490-13499.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.6.4.6

Activating Compound

Activating Compound Comment Organism Structure
additional information binding of substrates to the central pore of the Vps4 ATPase is activated by microtubule interacting and trafficking interacting motifs (MIMs) Saccharomyces cerevisiae
Vps2p helix 5 peptide C stimulates Vps4p ATPase activity and stabilizes the hexamer Saccharomyces cerevisiae

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of wild-type and mutant Vps4ps Saccharomyces cerevisiae

Protein Variants

Protein Variants Comment Organism
E233Q site-directed mutagenesis, an ATPase inactive mutant Saccharomyces cerevisiae
E243A site-directed mutagenesis, a pore loop mutant, displays essentially unchanged oligomerization, introducing E243A point mutation increases the affinity of peptide C binding by 3fold, shows reduced ATPase activity compared to the wild-type Saccharomyces cerevisiae
E243A/E247A site-directed mutagenesis, pore loop mutant, displays essentially unchanged oligomerization, the double mutant binds peptides 4fold (peptide C) or 10fold (peptide B) more tightly than wild-type Vps4p, shows reduced ATPase activity compared to the wild-type Saccharomyces cerevisiae
E247A site-directed mutagenesis, a pore loop mutant, displays essentially unchanged oligomerization, introducing E247A point mutation increases the affinity of peptide C binding by 4fold, shows reduced ATPase activity compared to the wild-type Saccharomyces cerevisiae
R241A site-directed mutagenesis, a pore loop 2 mutant, does not bind peptides with appreciable affinity Saccharomyces cerevisiae
R251A site-directed mutagenesis, a pore loop 2 adjacent mutant, does not bind peptides with appreciable affinity Saccharomyces cerevisiae
T240A site-directed mutagenesis, a pore loop mutant, displays essentially unchanged oligomerization Saccharomyces cerevisiae
T240F site-directed mutagenesis, a pore loop 2 mutant Saccharomyces cerevisiae
T240K site-directed mutagenesis, a pore loop 2 mutant Saccharomyces cerevisiae
T240V site-directed mutagenesis, a pore loop 2 mutant Saccharomyces cerevisiae
W206A site-directed mutagenesis, a pore loop 1 mutant, does not bind peptides with appreciable affinity Saccharomyces cerevisiae

Inhibitors

Inhibitors Comment Organism Structure
additional information binding of substrates to the central pore of the Vps4 ATPase is autoinhibited by the microtubule interacting and trafficking (MIT) domain, substrate engagement is autoinhibited by the Vps4p-MIT-domain and the inhibition is relieved by binding of either Type 1 or Type 2 MIM elements, which bind the Vps4p MIT domain through different interfaces Saccharomyces cerevisiae

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Saccharomyces cerevisiae

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + H2O Saccharomyces cerevisiae
-
 ADP + phosphate
-
 ?
additional information Saccharomyces cerevisiae residues from helix 5 of the Vps2p subunit of ESCRT-III bind to the central pore of an asymmetric Vps4p hexamer in a manner that is dependent upon the presence of flexible nucleotide analogues that can mimic multiple states in the ATP hydrolysis cycle, quantitative binding studies. Vps2p helix 5 peptides bind the Vps4p ATPase cassette. Vps4 substrates are initially recruited by an MIM-MIT interaction that activates the Vps4 central pore to engage substrates and generate force, thereby triggering ESCRT-III disassembly. The Vps4p hexamer binds a single peptide ?
-
 ?

Organism

Organism UniProt Comment Textmining
Saccharomyces cerevisiae P52917
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant wild-type and mutant Vps4ps Saccharomyces cerevisiae

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O
-
 Saccharomyces cerevisiae ADP + phosphate
-
 ?
additional information residues from helix 5 of the Vps2p subunit of ESCRT-III bind to the central pore of an asymmetric Vps4p hexamer in a manner that is dependent upon the presence of flexible nucleotide analogues that can mimic multiple states in the ATP hydrolysis cycle, quantitative binding studies. Vps2p helix 5 peptides bind the Vps4p ATPase cassette. Vps4 substrates are initially recruited by an MIM-MIT interaction that activates the Vps4 central pore to engage substrates and generate force, thereby triggering ESCRT-III disassembly. The Vps4p hexamer binds a single peptide Saccharomyces cerevisiae ?
-
 ?

Subunits

Subunits Comment Organism
hexamer eukaryotic Vps4 enzymes comprise the N-terminal MIT domain, an about 40-residue linker, a two-domain AAA ATPase cassette, a beta-domain that is inserted within the small domain of the ATPase cassette, and a C-terminal helix that binds against the large ATPase domain. Vps4 functions as a higher-order oligomer Saccharomyces cerevisiae

Synonyms

Synonyms Comment Organism
AAA ATPase Vps4
-
 Saccharomyces cerevisiae
Vps4 ATPase
-
 Saccharomyces cerevisiae
Vps4p
-
 Saccharomyces cerevisiae

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Saccharomyces cerevisiae

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Saccharomyces cerevisiae

General Information

General Information Comment Organism
evolution the enzyme Vps4 belongs to the type I AAA ATPases Saccharomyces cerevisiae
physiological function the endosomal sorting complexes required for transport (ESCRT) pathway drives reverse topology membrane fission events within multiple cellular pathways, including cytokinesis, multivesicular body biogenesis, repair of the plasma membrane, nuclear membrane vesicle formation, and HIV budding. The AAA ATPase Vps4 is recruited to membrane necks shortly before fission, where it catalyzes disassembly of the ESCRT-III lattice. Vps4 substrates are initially recruited by an MIM-MIT interaction that activates the Vps4 central pore to engage substrates and generate force, thereby triggering ESCRT-III disassembly. Vps2p helix 5 peptides bind the Vps4p ATPase cassette. Two-step model for disassembly of the ESCRT-III complex by Vps4, overview Saccharomyces cerevisiae