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A molecular and structural mechanism for G protein-mediated microtubule destabilization.


ABSTRACT: The heterotrimeric, G protein-coupled receptor-associated G protein, G?(s), binds tubulin with nanomolar affinity and disrupts microtubules in cells and in vitro. Here we determine that the activated form of G?(s) binds tubulin with a K(D) of 100 nm, stimulates tubulin GTPase, and promotes microtubule dynamic instability. Moreover, the data reveal that the ?3-?5 region of G?(s) is a functionally important motif in the G?(s)-mediated microtubule destabilization. Indeed, peptides corresponding to that region of G?(s) mimic G?(s) protein in activating tubulin GTPase and increase microtubule dynamic instability. We have identified specific mutations in peptides or proteins that interfere with this process. The data allow for a model of the G?(s)/tubulin interface in which G?(s) binds to the microtubule plus-end and activates the intrinsic tubulin GTPase. This model illuminates both the role of tubulin as an "effector" (e.g. adenylyl cyclase) for G?(s) and the role of G?(s) as a GTPase activator for tubulin. Given the ability of G?(s) to translocate intracellularly in response to agonist activation, G?(s) may play a role in hormone- or neurotransmitter-induced regulation of cellular morphology.

SUBMITTER: Dave RH 

PROVIDER: S-EPMC3039364 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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A molecular and structural mechanism for G protein-mediated microtubule destabilization.

Davé Rahul H RH   Saengsawang Witchuda W   Lopus Manu M   Davé Sonya S   Wilson Leslie L   Rasenick Mark M MM  

The Journal of biological chemistry 20101126 6


The heterotrimeric, G protein-coupled receptor-associated G protein, Gα(s), binds tubulin with nanomolar affinity and disrupts microtubules in cells and in vitro. Here we determine that the activated form of Gα(s) binds tubulin with a K(D) of 100 nm, stimulates tubulin GTPase, and promotes microtubule dynamic instability. Moreover, the data reveal that the α3-β5 region of Gα(s) is a functionally important motif in the Gα(s)-mediated microtubule destabilization. Indeed, peptides corresponding to  ...[more]

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