Short Linear Sequence Motif LxxPTPh Targets Diverse Proteins to Growing Microtubule Ends

Structure. 2017 Jun 6;25(6):924-932.e4. doi: 10.1016/j.str.2017.04.010. Epub 2017 May 25.


Microtubule plus-end tracking proteins (+TIPs) are involved in virtually all microtubule-based processes. End-binding (EB) proteins are considered master regulators of +TIP interaction networks, since they autonomously track growing microtubule ends and recruit a plethora of proteins to this location. Two major EB-interacting elements have been described: CAP-Gly domains and linear SxIP sequence motifs. Here, we identified LxxPTPh as a third EB-binding motif that enables major +TIPs to interact with EBs at microtubule ends. In contrast to EB-SxIP and EB-CAP-Gly, the EB-LxxPTPh binding mode does not depend on the C-terminal tail region of EB. Our study reveals that +TIPs developed additional strategies besides CAP-Gly and SxIP to target EBs at growing microtubule ends. They further provide a unique basis to discover novel +TIPs, and to dissect the role of key interaction nodes and their differential regulation for hierarchical +TIP network organization and function in eukaryotic organisms.

Keywords: X-ray crystallography; end-binding proteins; linear motif; microtubule plus-end tracking proteins; molecular mechanism; structure-function relationship.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • COS Cells
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chlorocebus aethiops
  • Crystallography, X-Ray
  • Fluorescence Polarization
  • Microtubule Proteins / chemistry
  • Microtubule Proteins / genetics
  • Microtubule Proteins / metabolism
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Models, Molecular
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Domains
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • BIM1 protein, S cerevisiae
  • Cell Cycle Proteins
  • KAR9 protein, S cerevisiae
  • Microtubule Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins