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#proton pumps

2 public questions tagged with this topic.

Membrane Transportation

F-type ATPases differ from other ATPases because they:

F-type ATPases, historically termed FoF1 ATP synthases, represent an evolutionary unique class of rotary translocases that normally synthesize rather than consume ATP. While P-type and V-type pumps hydrolyze ATP to build H+ or Ca2+ gradients, F-type complexes harness pre-existing proton motive force created by electron transport chains in mitochondria, chloroplast thylakoids, and bacterial plasma membranes. The membrane-embedded Fo sector contains an oligomeric c-ring that binds protons via conserved carboxylate, rotating against subunit a as protons move down gradient. This rotation drives the central gamma-epsilon stalk inside the alpha3beta3 F1 hexamer, forcing beta subunits through open, loose and tight conformations that bind ADP and inorganic phosphate and condense them into ATP via binding-change mechanism. Isolated enzymes reversibly hydrolyze ATP to pump protons when proton motive force collapses, but physiological role is ATP production, supplying bulk of cellular ATP for biosynthesis, motility and transport work. Such chemiosmotic coupling explains oxidative phosphorylation and photophosphorylation efficiency.

Ref: Stock et al., Curr Opin Struct Biol 2000, ATP synthase rotary mechanism; Alberts, Chapter 14.

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Cell Organelles

The acidic pH of lysosomes is maintained by:

Lysosomes maintain a highly acidic lumen essential for optimal activity of about sixty acid hydrolases involved in macromolecular digestion and for solute transport. The steep proton gradient, pH 4.5 to 5.0 inside versus cytosolic pH 7.2, representing over two pH units and hundredfold proton concentration difference, is actively generated by vacuolar-type H+ ATPase, V-ATPase, consuming ATP. This massive multi-subunit rotary pump consists of peripheral V1 domain with A3B3 hexamer that hydrolyzes ATP and integral V0 domain forming proton channel with c-ring rotation. ATP hydrolysis drives rotation of central stalk and c-ring, translocating protons into the lumen against electrochemical gradient at cost of one ATP per two to three protons. Counterion movement of chloride via ClC-7 Cl-/H+ exchanger and potassium channel provides electroneutrality and osmotic balance preventing excessive membrane potential. Resulting acidity activates cathepsins B, D, L and others by protonation of catalytic residues, induces conformational changes releasing enzymes from mannose-6-phosphate receptors after delivery, and denatures substrates improving access. Low pH also prevents hydrolase leakage from causing cytosolic damage. Inhibition by bafilomycin A1 or concanamycin neutralizes lysosomes, blocking degradation, autophagy flux, and cholesterol egress from NPC1 pathway.

Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Chapter 13: Lysosomes – V-ATPase and Acidification.

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