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
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Mentions: Averaging B lattice contacts of the Mal3 CH domain on GTPγS microtubules produced an 8.6 Å resolution reconstruction in which the secondary structural elements of tubulin and the CH domain of Mal3 are clearly resolved (Figure 2A, gray and green envelope, respectively; Figure S2; Movie S1). This subnanometer resolution allowed α- and β-tubulins to be distinguished unambiguously (Figure 2B) and a pseudoatomic model of the Mal3-binding site to be generated (Figure 2D). The Mal3 CH domain contacts four different tubulin dimers (Figures 2A and 2C), providing an explanation for how the CH domain distinguishes between B lattice contacts and the microtubule seam: the binding site is formed by two adjacent α-tubulin contacts (toward the microtubule plus end) and two adjacent β-tubulin contacts (toward the minus end). This configuration is not present at the seam where lateral α-β contacts exist (Figure 2C). In binding between protofilaments, the EB footprint is distinct from that of microtubule-based motors kinesin and dynein, which step along the protofilament ridge (Mizuno et al., 2004).
Affiliation: Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.