Structural basis of microtubule plus end tracking by XMAP215, CLIP-170, and EB1.
Microtubule plus end binding proteins (+TIPs) localize to the dynamic plus ends of microtubules, where they stimulate microtubule growth and recruit signaling molecules. Three main +TIP classes have been identified (XMAP215, EB1, and CLIP-170), but whether they act upon microtubule plus ends through a similar mechanism has not been resolved. Here, we report crystal structures of the tubulin binding domains of XMAP215 (yeast Stu2p and Drosophila Msps), EB1 (yeast Bim1p and human EB1), and CLIP-170 (human), which reveal diverse tubulin binding interfaces. Functional studies, however, reveal a common property that native or artificial dimerization of tubulin binding domains (including chemically induced heterodimers of EB1 and CLIP-170) induces tubulin nucleation/assembly in vitro and, in most cases, plus end tracking in living cells. We propose that +TIPs, although diverse in structure, share a common property of multimerizing tubulin, thus acting as polymerization chaperones that aid in subunit addition to the microtubule plus end.
Slep
Kevin C
KC
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Vale
Ronald D
RD
D000818:Animals; D001692:Biological Transport; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry*; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D019281:Dimerization; D029721:Drosophila Proteins / Q000737:chemistry; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D008868:Microtubule Proteins / Q000737:chemistry*; D008869:Microtubule-Associated Proteins / Q000737:chemistry*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D008941:Spindle Apparatus; D040681:Structural Homology, Protein; D013997:Time Factors; D000096985:Calponins
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D029701:Saccharomyces cerevisiae Proteins; D000096985:Calponins; C119683:BIM1 protein, S cerevisiae; C405804:EB1 microtubule binding proteins; C109414:STU2 protein, S cerevisiae; C121511:msps protein, Drosophila; C076744:cytoplasmic linker protein 170