Bilayer Mechanical Properties Regulate Transmembrane Helix Mobility and Enzymatic State of CD39
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https://doi.org/10.1021/bi061052pMetadata
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Grinthal, Alison, and Guido Guidotti. 2007. Bilayer mechanical properties regulate transmembrane helix mobility and enzymatic state of CD39. Biochemistry 46(1): 279-290.Abstract
CD39 can exist in at least two distinct functional states depending on the presence and intact membrane integration of its two transmembrane helices. In native membranes, the transmembrane helices undergo dynamic rotational motions that are required for enzymatic activity and are regulated by substrate binding. In the present study we show that bilayer mechanical properties regulate conversion between the two enzymatic functional states by modulating transmembrane helix dynamics. Alteration of membrane properties by insertion of cone shaped or inverse cone shaped amphiphiles or by cholesterol removal switches CD39 to the same enzymatic state as does removing or solubilizing the transmembrane domains. The same membrane alterations increase the propensity of both transmembrane helices to rotate within the packed structure, resulting in a structure with greater mobility but not an altered primary conformation. Membrane alteration also abolishes the ability of substrate to stabilize the helices in their primary conformation, indicating a loss of coupling between substrate binding and transmembrane helix dynamics. Removal of either transmembrane helix mimics the effect of membrane alteration on the mobility and substrate sensitivity of the remaining helix, suggesting that the ends of the extracellular domain have intrinsic flexibility. We suggest that a mechanical bilayer property, potentially elasticity, regulates CD39 by altering the balance between stability and flexibility of its transmembrane helices and, in turn, of its active site.Citable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11028289
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