Structure and function relationship of A- and V-ATPases

• Applicant: Professor Dr. Gerhard Grüber, until 8/2005
• Subject Area: Biochemistry
• Term: from 2001 to 2005
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5348012

ATP synthases/ATP hydrolases are present in every organism and are essentiel for every living cell. A1AO-, F1FO- and V1VO ATPases are composed of a head and a base connected by stalks. Phylogenetic studies show that A- and V-ATPases evolved from a common anchestor. The evolutionary relationship of both enzymes was confirmed by comparing the low-resolution structure of the A1 (Methanosarcina mazei Gö1), F1 (Escherichia coli) and V1 ATPase (Manduca sexta) revealing a knob-and-stalk-like feature. The stalk domains of the closer related A1 and V1 are remarkably similar in shape and dimensions, which, in contrast, has different structural features in the F1 ATPase. Despite the differences in structure, the A1AO and F1FO enzymes function as ATP synthases in cells whereas the V1VO ATPase works as an ATP-driven ion pump. The A- and V-ATPases are thought to undergo conformational changes as ATP binds, is hydrolyzed, and its product are released. With a quaternary structure, a two- and/or three-dimensional reconstruction of the A1 and V1 complex, and three-dimensional crystals of the nucleotide-binding subunit of V1 already in hand, the questions about the structure/function relationship in A- and V-ATPases and how the energy coupling between the A1/V1 and AO/VO domains is coupled by their stalks will be addressed.

• DFG Programme: Research Grants