title: Role of the carboxy terminal region of beta tubulin on microtubule dynamics through its interaction with the GTP phosphate binding region.
abstract: The dynamic instability of microtubules depends on the GTP binding to tubulin, the rate of hydrolysis of GTP bound to tubulin molecules, at the microtubule caps, and on the affinity and exchange rate of tubulin for GTP versus GDP. It has been demonstrated that the binding of microtubule-associated proteins (MAPs) such as Tau or MAP2 notably enhances microtubule stability in vivo. These MAPs bind to the tubulin carboxy terminal domain. Consequently, an attractive hypothesis to explain the modulation of microtubule dynamics by MAPs is that the carboxy terminal domain of tubulin interacts with a region close to the GTP binding site, preventing the binding of GTP or exchange of GDP for GTP. By carrying out a combined analysis of crosslinking and limited proteolysis, an intramolecular interaction between the carboxy terminus and the tubulin region containing the GTP binding site in beta tubulin has been observed. It is proposed that this interaction modifies the binding of GTP to the tubulin beta-subunit and, therefore, affects tubulin assembly dynamics. This suggests a molecular explanation for the effect of MAPs in facilitating tubulin polymerization through the regulation of the interaction of GTP.
authors.affiliation: Centro de Biología Molecular (CSIC-UAM), Universidad Autónoma, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Padilla
authors.forename: C
authors.initials: C
authors.lastname: López Otin
authors.forename: L
authors.initials: L
authors.lastname: Serrano
authors.forename: J
authors.initials: J
authors.lastname: Avila
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003432:Cross-Linking Reagents; D005022:Ethyldimethylaminopropyl Carbodiimide; D006160:Guanosine Triphosphate / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D010710:Phosphates / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D010710:Phosphates; D014404:Tubulin; D006160:Guanosine Triphosphate; D005022:Ethyldimethylaminopropyl Carbodiimide