M O Steinmetz

Summary

Affiliation: Paul Scherrer Institute
Country: Switzerland

Publications

  1. Balaguer F, Mühlethaler T, Estévez Gallego J, Calvo E, Giménez Abián J, Risinger A, et al. Crystal Structure of the Cyclostreptin-Tubulin Adduct: Implications for Tubulin Activation by Taxane-Site Ligands. Int J Mol Sci. 2019;20: pubmed publisher
    ..This supports the idea that overexpression of βIII increases microtubule dynamicity by counteracting the enhanced microtubule stability promoted by covalent taxane-site binding ligands. ..
  2. Prota A, Danel F, Bachmann F, Bargsten K, Buey R, Pohlmann J, et al. The novel microtubule-destabilizing drug BAL27862 binds to the colchicine site of tubulin with distinct effects on microtubule organization. J Mol Biol. 2014;426:1848-60 pubmed publisher
    ..Taken together, our data define BAL27862 as a potent, colchicine site-binding, microtubule-destabilizing agent with distinct effects on microtubule organization. ..
  3. Steinmetz M, Prota A. Microtubule-Targeting Agents: Strategies To Hijack the Cytoskeleton. Trends Cell Biol. 2018;28:776-792 pubmed publisher
    ..We further formulate some outstanding questions related to MTA structural biology and present possible routes for future investigations of this fascinating class of antimitotic agents. ..
  4. Prota A, Bargsten K, Diaz J, Marsh M, Cuevas C, Liniger M, et al. A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs. Proc Natl Acad Sci U S A. 2014;111:13817-21 pubmed publisher
    ..They further provide a structural basis for the rational design of potent microtubule-destabilizing agents, thus opening opportunities for the development of next-generation ADCs for the treatment of cancer. ..
  5. Menchon G, Prota A, Lucena Agell D, Bucher P, Jansen R, Irschik H, et al. A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin. Nat Commun. 2018;9:2106 pubmed publisher
    ..Our study provides a basis for the discovery and development of next-generation MTAs for the treatment of cancer. ..
  6. Steinmetz M, Akhmanova A. Capturing protein tails by CAP-Gly domains. Trends Biochem Sci. 2008;33:535-45 pubmed publisher
    ..It is becoming increasingly clear that CAP-Gly domains are also involved in coordinating complex and diverse aspects of cell architecture and signalling. ..
  7. Stangier M, Kumar A, Chen X, Farcas A, Barral Y, Steinmetz M. Structure-Function Relationship of the Bik1-Bim1 Complex. Structure. 2018;26:607-618.e4 pubmed publisher
    ..Our results provide insight into the role of the Bik1-Bim1 interaction for cell division, and demonstrate that the CLIP-170-EB1 module is evolutionarily flexible. ..
  8. Prota A, Setter J, Waight A, Bargsten K, Murga J, Díaz J, et al. Pironetin Binds Covalently to ?Cys316 and Perturbs a Major Loop and Helix of ?-Tubulin to Inhibit Microtubule Formation. J Mol Biol. 2016;428:2981-8 pubmed publisher
    ..They further extend our knowledge on strategies evolved by natural products to target and perturb the microtubule cytoskeleton. ..
  9. Doodhi H, Prota A, Rodríguez García R, Xiao H, Custar D, Bargsten K, et al. Termination of Protofilament Elongation by Eribulin Induces Lattice Defects that Promote Microtubule Catastrophes. Curr Biol. 2016;26:1713-1721 pubmed publisher
    ..Because EB3 comet splitting was also observed in control microtubules in the absence of any drugs, we propose that Eribulin amplifies a natural pathway toward catastrophe by promoting the arrest of protofilament elongation. ..

More Information

Publications18

  1. Jiang K, Faltova L, Hua S, Capitani G, Prota A, Landgraf C, et al. Structural Basis of Formation of the Microtubule Minus-End-Regulating CAMSAP-Katanin Complex. Structure. 2018;26:375-382.e4 pubmed publisher
    ..Our work provides a general molecular mechanism for the cooperation of katanin with major microtubule minus-end regulators. ..
  2. Kraatz S, Guichard P, Obbineni J, Olieric N, Hatzopoulos G, Hilbert M, et al. The Human Centriolar Protein CEP135 Contains a Two-Stranded Coiled-Coil Domain Critical for Microtubule Binding. Structure. 2016;24:1358-1371 pubmed publisher
    ..Our results provide the first structural information on CEP135/Bld10p proteins and offer insights into their microtubule-binding mechanism. ..
  3. Rezabkova L, Jiang K, Capitani G, Prota A, Akhmanova A, Steinmetz M, et al. Structural basis of katanin p60:p80 complex formation. Sci Rep. 2017;7:14893 pubmed publisher
    ..Moreover, p60-MIT was compared with other MIT domain structures and similarities are discussed. ..
  4. Sharma A, Sáez Calvo G, Olieric N, de Asís Balaguer F, Barasoain I, Lamberth C, et al. Quinolin-6-Yloxyacetamides Are Microtubule Destabilizing Agents That Bind to the Colchicine Site of Tubulin. Int J Mol Sci. 2017;18: pubmed publisher
    ..They further extend our structural knowledge on antitubulin agents and thus should aid in the development of new strategies for the rational design of ligands against multidrug-resistant cancer cells. ..
  5. Kumar A, Manatschal C, Rai A, Grigoriev I, Degen M, Jaussi R, et al. Short Linear Sequence Motif LxxPTPh Targets Diverse Proteins to Growing Microtubule Ends. Structure. 2017;25:924-932.e4 pubmed publisher
    ..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. ..
  6. Steinmetz M, Jahnke W, Towbin H, Garcia Echeverria C, Voshol H, Muller D, et al. Phosphorylation disrupts the central helix in Op18/stathmin and suppresses binding to tubulin. EMBO Rep. 2001;2:505-10 pubmed
    ..Together, our findings have implications for the prediction of phosphorylation sites and give insights into the molecular behavior of a globally disordered protein. ..
  7. Sharma A, Aher A, Dynes N, Frey D, Katrukha E, Jaussi R, et al. Centriolar CPAP/SAS-4 Imparts Slow Processive Microtubule Growth. Dev Cell. 2016;37:362-376 pubmed publisher
    ..Our results suggest that CPAP acts as a molecular lid that ensures slow assembly of centriolar microtubules and, thereby, contributes to organelle length control. ..
  8. Steinmetz M, Jelesarov I, Matousek W, Honnappa S, Jahnke W, Missimer J, et al. Molecular basis of coiled-coil formation. Proc Natl Acad Sci U S A. 2007;104:7062-7 pubmed
    ..Our findings provide a general explanation for the molecular mechanism of coiled-coil formation. ..
  9. request reprint
    Steinmetz M. Structure and thermodynamics of the tubulin-stathmin interaction. J Struct Biol. 2007;158:137-47 pubmed
    ..Based on these and on functional information I formulate an updated molecular mechanism on how tubulin-binding by stathmin regulates microtubule dynamics. ..