ATPase

ATPases (EC 3.6.1.3, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca²⁺ + Mg²⁺)-ATPase, HCO₃⁻-ATPase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion^{[1][2][3][4][5][6]} or the inverse reaction. This dephosphorylation reaction releases energy, which the enzyme (in most cases) harnesses to drive other chemical reactions that would not otherwise occur. This process is widely used in all known forms of life.

Some such enzymes are

Functions

Transmembrane ATPases import metabolites necessary for

"The membrane-bound copper transporting adenosine triphosphatase (Cu-ATPase), which selectively binds copper ions, transports copper ions into and out of cells (Harris et al. 1998)." Source: https://www.atsdr.cdc.gov/ToxProfiles/tp132.pdf p. 73

Structure

The Walker motifs are a telltale protein sequence motif for nucleotide binding and hydrolysis. Beyond this broad function, the Walker motifs can be found in almost all natural ATPases, with the notable exception of tyrosine kinases.^[9] The Walker motifs commonly form a Beta sheet-turn-Alpha helix that is self-organized as a Nest (protein structural motif). This is thought to be because modern ATPases evolved from small NTP-binding peptides that had to be self-organized.^[10]

Protein design has been able to replicate the ATPase function (weakly) without using natural ATPase sequences or structures. Importantly, while all natural ATPases have some beta-sheet structure, the designed "Alternative ATPase" lacks beta sheet structure, demonstrating that this life-essential function is possible with sequences and structures not found in nature.^[11]

Mechanism

ATPase (also called F₀F₁-ATP Synthase) is a charge-transferring complex that catalyzes ATP to perform ATP synthesis by moving ions through the membrane.^[12]

The coupling of ATP hydrolysis and transport is a chemical reaction in which a fixed number of solute molecules are transported for each ATP molecule hydrolyzed; for the Na⁺/K⁺ exchanger, this is three Na⁺ ions out of the cell and two K+ ions inside per ATP molecule hydrolyzed.

Transmembrane ATPases make use of ATP's chemical potential energy by performing mechanical work: they transport solutes in the opposite direction of their thermodynamically preferred direction of movement—that is, from the side of the membrane with low concentration to the side with high concentration. This process is referred to as active transport.

For instance, inhibiting vesicular H⁺-ATPases would result in a rise in the pH within vesicles and a drop in the pH of the cytoplasm.

All of the ATPases share a common basic structure. Each rotary ATPase is composed of two major components: F₀/A₀/V₀ and F₁/A₁/V₁. They are connected by 1-3 stalks to maintain stability, control rotation, and prevent them from rotating in the other direction. One stalk is utilized to transmit torque.^[13] The number of peripheral stalks is dependent on the type of ATPase: F-ATPases have one, A-ATPases have two, and V-ATPases have three. The F₁ catalytic domain is located on the N-side of the membrane and is involved in the synthesis and degradation of ATP and is involved in oxidative phosphorylation. The F₀ transmembrane domain is involved in the movement of ions across the membrane.^[12]

The bacterial F₀F₁-ATPase consists of the soluble F₁ domain and the transmembrane F₀ domain, which is composed of several subunits with varying stoichiometry. There are two subunits, γ, and ε, that form the central stalk and they are linked to F₀. F₀ contains a c-subunit oligomer in the shape of a ring (c-ring). The α subunit is close to the subunit b₂ and makes up the stalk that connects the transmembrane subunits to the α3β3 and δ subunits. F-ATP synthases are identical in appearance and function except for the mitochondrial F₀F₁-ATP synthase, which contains 7-9 additional subunits.^[12]

The electrochemical potential is what causes the c-ring to rotate in a clockwise direction for ATP synthesis. This causes the central stalk and the catalytic domain to change shape. Rotating the c-ring causes three ATP molecules to be made, which then causes H⁺ to move from the P-side of the membrane to the N-side of the membrane. The counterclockwise rotation of the c-ring is driven by ATP hydrolysis and ions move from the N-side to the P-side, which helps to build up electrochemical potential.^[12]

Transmembrane ATP synthases

The

• Rotary ATPases[14]^[15]
  • plasma membranes are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).^[16]
    • F-ATPases lacking a
      N-ATPases, since they seem to form a distinct group that is further apart from usual F-ATPases than A-ATPases are from V-ATPases.^[17]
  • V-ATPases (V1VO-ATPases) are primarily found in eukaryotic vacuoles, catalysing ATP hydrolysis to transport solutes and lower pH in organelles like proton pump of lysosome.
  • A-ATPases (A1AO-ATPases) are found in Archaea
    and some extremophilic bacteria. They are arranged like V-ATPases, but function like F-ATPases mainly as ATP synthases.
  • Many homologs that are not necessarily rotaty exist. See ATP synthase § Evolution.
• P-ATPases
  (E1E2-ATPases) are found in bacteria, fungi and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.
• E-ATPases are
  CD39s, and ecto-ATP/Dases, all of which are members of a "GDA1 CD39" superfamily.^[18]
• P-loop NTPases
  .

• ATP1A1, ATP1A2, ATP1A3, ATP1A4, ATP1B1, ATP1B2, ATP1B3, ATP1B4
• Ca⁺⁺ transporting: ATP2A1, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, ATP2C1, ATP2C2
• ATP3
• H⁺/K⁺ exchanging: ATP4A
• ATP5O, ATP5S, MT-ATP6, MT-ATP8
• ATP6V0A1, ATP6V0A2, ATP6V0A4, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V0D2, ATP6V0E
• Cu⁺⁺ transporting:
  ATP7B
• Class I, type 8:
  ATP8B1, ATP8B2, ATP8B3, ATP8B4
• Class II, type 9: ATP9A, ATP9B
• Class V, type 10:
  ATP10A, ATP10B, ATP10D
• Class VI, type 11: ATP11A, ATP11B, ATP11C
• H⁺/K⁺ transporting, nongastric: ATP12A
• type 13: ATP13A1, ATP13A2, ATP13A3, ATP13A4, ATP13A5

See also

• ATP synthase
• ATP synthase alpha/beta subunits
• AAA proteins
• P-ATPase

References

External links

Wikimedia Commons has media related to Adenosine triphosphatases.

• "ATP synthase - a splendid molecular machine"
• ATPase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Electron microscopy structures of ATPases from the EM Data Bank(EMDB)