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EBs recognize a nucleotide-dependent structural cap at growing microtubule ends.

Maurer SP, Fourniol FJ, Bohner G, Moores CA, Surrey T - Cell (2012)

Bottom Line: By binding close to the exchangeable GTP-binding site, the CH domain is ideally positioned to sense the microtubule's nucleotide state.The same microtubule-end region is also a stabilizing structural cap protecting the microtubule from depolymerization.This insight supports a common structural link between two important biological phenomena, microtubule dynamic instability and end tracking.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.

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Comparison between the EB-Tubulin and G-Protein-GAP Complexes, Related to Figure 3(A) Pseudoatomic model of Mal3-microtubule interaction (Mal3 CH model, rainbow-colored ribbons) showing α2-tubulin (blue), β3-tubulin (cyan), and GTPγS (ball-and-stick model). The putative switch II T3-H3 motif of β-tubulin is highlighted in magenta.(B) Structure of small G protein Ras (PDB 1WQ1) (cyan) complexed with Mg.GDP.AlF3 (ball and stick) bound to RasGAP (rainbow-colored ribbons) (Scheffzek et al., 1997). The Ras switch II motif is highlighted in magenta.(C) Structure of the heterotrimeric G protein Giα1 (PDB 1AGR) (cyan) complexed with Mg.GDP.AlF4 (ball and stick) bound to its GAP RGS4 (rainbow-colored ribbons) (Tesmer et al., 1997). The Giα1 switch II motif is highlighted in magenta. Whereas the GAPs of small G proteins such as Ras contribute catalytic residues to the GTPase reaction, the GAPs of heterotrimeric G proteins act indirectly by stabilizing the switch region of the catalytic Gα subunit, thereby stabilizing the catalytic transition state of GTP hydrolysis. The comparable binding site of EBs with respect to the β-tubulin catalytic site suggests that EBs could play an equivalent role.
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figs6: Comparison between the EB-Tubulin and G-Protein-GAP Complexes, Related to Figure 3(A) Pseudoatomic model of Mal3-microtubule interaction (Mal3 CH model, rainbow-colored ribbons) showing α2-tubulin (blue), β3-tubulin (cyan), and GTPγS (ball-and-stick model). The putative switch II T3-H3 motif of β-tubulin is highlighted in magenta.(B) Structure of small G protein Ras (PDB 1WQ1) (cyan) complexed with Mg.GDP.AlF3 (ball and stick) bound to RasGAP (rainbow-colored ribbons) (Scheffzek et al., 1997). The Ras switch II motif is highlighted in magenta.(C) Structure of the heterotrimeric G protein Giα1 (PDB 1AGR) (cyan) complexed with Mg.GDP.AlF4 (ball and stick) bound to its GAP RGS4 (rainbow-colored ribbons) (Tesmer et al., 1997). The Giα1 switch II motif is highlighted in magenta. Whereas the GAPs of small G proteins such as Ras contribute catalytic residues to the GTPase reaction, the GAPs of heterotrimeric G proteins act indirectly by stabilizing the switch region of the catalytic Gα subunit, thereby stabilizing the catalytic transition state of GTP hydrolysis. The comparable binding site of EBs with respect to the β-tubulin catalytic site suggests that EBs could play an equivalent role.

Mentions: At high concentrations, Mal3 has been observed to reduce the lifetime of its own binding site—i.e., the extended stabilizing region at growing microtubule ends—by up to a factor of two (Maurer et al., 2011). In this context it is interesting to note that the interaction between EBs and GTPγS microtubules is structurally reminiscent of the GTPase-activating proteins (GAPs) of G proteins, which are molecular switches in cell-signaling circuits (Figure S6) (Vetter and Wittinghofer, 2001). In particular, the GAPs of heterotrimeric G proteins stimulate the basal GTPase activity of their cognate Gα protein. Thus, β-tubulin helix H3 might be functionally equivalent to the switch II helix in other GTPases, as previously suggested (Nogales et al., 1999). This structural analogy supports the possibility that EBs might recognize a conformational state of the microtubule lattice induced by or during GTP hydrolysis. Future studies will be aimed at testing this intriguing hypothesis.


EBs recognize a nucleotide-dependent structural cap at growing microtubule ends.

Maurer SP, Fourniol FJ, Bohner G, Moores CA, Surrey T - Cell (2012)

Comparison between the EB-Tubulin and G-Protein-GAP Complexes, Related to Figure 3(A) Pseudoatomic model of Mal3-microtubule interaction (Mal3 CH model, rainbow-colored ribbons) showing α2-tubulin (blue), β3-tubulin (cyan), and GTPγS (ball-and-stick model). The putative switch II T3-H3 motif of β-tubulin is highlighted in magenta.(B) Structure of small G protein Ras (PDB 1WQ1) (cyan) complexed with Mg.GDP.AlF3 (ball and stick) bound to RasGAP (rainbow-colored ribbons) (Scheffzek et al., 1997). The Ras switch II motif is highlighted in magenta.(C) Structure of the heterotrimeric G protein Giα1 (PDB 1AGR) (cyan) complexed with Mg.GDP.AlF4 (ball and stick) bound to its GAP RGS4 (rainbow-colored ribbons) (Tesmer et al., 1997). The Giα1 switch II motif is highlighted in magenta. Whereas the GAPs of small G proteins such as Ras contribute catalytic residues to the GTPase reaction, the GAPs of heterotrimeric G proteins act indirectly by stabilizing the switch region of the catalytic Gα subunit, thereby stabilizing the catalytic transition state of GTP hydrolysis. The comparable binding site of EBs with respect to the β-tubulin catalytic site suggests that EBs could play an equivalent role.
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Related In: Results  -  Collection

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Show All Figures
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figs6: Comparison between the EB-Tubulin and G-Protein-GAP Complexes, Related to Figure 3(A) Pseudoatomic model of Mal3-microtubule interaction (Mal3 CH model, rainbow-colored ribbons) showing α2-tubulin (blue), β3-tubulin (cyan), and GTPγS (ball-and-stick model). The putative switch II T3-H3 motif of β-tubulin is highlighted in magenta.(B) Structure of small G protein Ras (PDB 1WQ1) (cyan) complexed with Mg.GDP.AlF3 (ball and stick) bound to RasGAP (rainbow-colored ribbons) (Scheffzek et al., 1997). The Ras switch II motif is highlighted in magenta.(C) Structure of the heterotrimeric G protein Giα1 (PDB 1AGR) (cyan) complexed with Mg.GDP.AlF4 (ball and stick) bound to its GAP RGS4 (rainbow-colored ribbons) (Tesmer et al., 1997). The Giα1 switch II motif is highlighted in magenta. Whereas the GAPs of small G proteins such as Ras contribute catalytic residues to the GTPase reaction, the GAPs of heterotrimeric G proteins act indirectly by stabilizing the switch region of the catalytic Gα subunit, thereby stabilizing the catalytic transition state of GTP hydrolysis. The comparable binding site of EBs with respect to the β-tubulin catalytic site suggests that EBs could play an equivalent role.
Mentions: At high concentrations, Mal3 has been observed to reduce the lifetime of its own binding site—i.e., the extended stabilizing region at growing microtubule ends—by up to a factor of two (Maurer et al., 2011). In this context it is interesting to note that the interaction between EBs and GTPγS microtubules is structurally reminiscent of the GTPase-activating proteins (GAPs) of G proteins, which are molecular switches in cell-signaling circuits (Figure S6) (Vetter and Wittinghofer, 2001). In particular, the GAPs of heterotrimeric G proteins stimulate the basal GTPase activity of their cognate Gα protein. Thus, β-tubulin helix H3 might be functionally equivalent to the switch II helix in other GTPases, as previously suggested (Nogales et al., 1999). This structural analogy supports the possibility that EBs might recognize a conformational state of the microtubule lattice induced by or during GTP hydrolysis. Future studies will be aimed at testing this intriguing hypothesis.

Bottom Line: By binding close to the exchangeable GTP-binding site, the CH domain is ideally positioned to sense the microtubule's nucleotide state.The same microtubule-end region is also a stabilizing structural cap protecting the microtubule from depolymerization.This insight supports a common structural link between two important biological phenomena, microtubule dynamic instability and end tracking.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.

Show MeSH