EBs recognize a nucleotide-dependent structural cap at growing microtubule ends.
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.
Affiliation: Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.Show MeSH
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.
Affiliation: Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.