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Mycobacterium smegmatis ATP synthase Fo combined all classes
Structural highlights
FunctionA0R205_MYCS2 F(1)F(0) ATP synthase produces ATP from ADP in the presence of a proton or sodium gradient. F-type ATPases consist of two structural domains, F(1) containing the extramembraneous catalytic core and F(0) containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation.[ARBA:ARBA00025198][HAMAP-Rule:MF_01396] Key component of the F(0) channel; it plays a direct role in translocation across the membrane. A homomeric c-ring of between 10-14 subunits forms the central stalk rotor element with the F(1) delta and epsilon subunits.[HAMAP-Rule:MF_01396] Publication Abstract from PubMedThe structure has been determined by electron cryomicroscopy of the adenosine triphosphate (ATP) synthase from Mycobacterium smegmatis This analysis confirms features in a prior description of the structure of the enzyme, but it also describes other highly significant attributes not recognized before that are crucial for understanding the mechanism and regulation of the mycobacterial enzyme. First, we resolved not only the three main states in the catalytic cycle described before but also eight substates that portray structural and mechanistic changes occurring during a 360 degrees catalytic cycle. Second, a mechanism of auto-inhibition of ATP hydrolysis involves not only the engagement of the C-terminal region of an alpha-subunit in a loop in the gamma-subunit, as proposed before, but also a "fail-safe" mechanism involving the b'-subunit in the peripheral stalk that enhances engagement. A third unreported characteristic is that the fused bdelta-subunit contains a duplicated domain in its N-terminal region where the two copies of the domain participate in similar modes of attachment of the two of three N-terminal regions of the alpha-subunits. The auto-inhibitory plus the associated "fail-safe" mechanisms and the modes of attachment of the alpha-subunits provide targets for development of innovative antitubercular drugs. The structure also provides support for an observation made in the bovine ATP synthase that the transmembrane proton-motive force that provides the energy to drive the rotary mechanism is delivered directly and tangentially to the rotor via a Grotthuss water chain in a polar L-shaped tunnel. Structure of the ATP synthase from Mycobacterium smegmatis provides targets for treating tuberculosis.,Montgomery MG, Petri J, Spikes TE, Walker JE Proc Natl Acad Sci U S A. 2021 Nov 23;118(47):e2111899118. doi: , 10.1073/pnas.2111899118. PMID:34782468[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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