title: Centromere protein F includes two sites that couple efficiently to depolymerizing microtubules.
abstract: Firm attachments between kinetochores and dynamic spindle microtubules (MTs) are important for accurate chromosome segregation. Centromere protein F (CENP-F) has been shown to include two MT-binding domains, so it may participate in this key mitotic process. Here, we show that the N-terminal MT-binding domain of CENP-F prefers curled oligomers of tubulin relative to MT walls by approximately fivefold, suggesting that it may contribute to the firm bonds between kinetochores and the flared plus ends of dynamic MTs. A polypeptide from CENP-F's C terminus also bound MTs, and either protein fragment diffused on a stable MT wall. They also followed the ends of dynamic MTs as they shortened. When either fragment was coupled to a microbead, the force it could transduce from a shortening MT averaged 3-5 pN but could exceed 10 pN, identifying CENP-F as a highly effective coupler to shortening MTs.
authors.affiliation: Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia, 119991 Laboratory of Biophysics, Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia, 117513 N. F. Gamaleya Research Institute for Epidemiology and Microbiology, Moscow, Russia, 123098.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Volkov
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Grissom
authors.affiliation: Department of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia, 119991.
authors.forename: Vladimir K
authors.initials: VK
authors.lastname: Arzhanik
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Anatoly V
authors.initials: AV
authors.lastname: Zaytsev
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309.
authors.forename: Kutralanathan
authors.initials: K
authors.lastname: Renganathan
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309.
authors.forename: Tristan
authors.initials: T
authors.lastname: McClure-Begley
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309.
authors.forename: William M
authors.initials: WM
authors.lastname: Old
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309.
authors.forename: Natalie
authors.initials: N
authors.lastname: Ahn
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309 richard.mcintosh@colorado.edu.
authors.forename: J Richard
authors.initials: JR
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics*; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics; D058105:Polymerization; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D008840:Microfilament Proteins; D014404:Tubulin; C094772:centromere protein F