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, Arp2/3, n = 262

, Arp2/3+Gmf1, n = 731

. Arp2/3+arpin, , 1130.

, Arrows highlight the visible new masses, which likely represent the globular ?-propeller domains of a Crn1 dimer. Scale bar, 10 nm. Cartoon (right) depicts proposed arrangement of two Crn1 molecules (dark blue) dimerized by GST (green dots)

, Arp2/3 complex [14] filtered to 25 Å resolution using UCSF Chimera, vol.51

, Arrows highlight the position of GMF (grey) bound to Arp2 and p40/ARPC1 subunits. (C,D) Three-dimensional reconstructions of Gmf1-bound Arp2/3 complex in the standard open conformation (C) and the new open conformation (D), Arp2/3 complex subunits, colorcoded and labeled as in Figure 1A, vol.10

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, Tankyrase1/2 is necessary for inhibitory activity of Arpin Arp2/3 complex is the key machinery that drives the growth of branched actin network and

, Arpin is a recently found inhibitor of Arp2/3 complex that counteract WAVE complex

, GTPase Rac as well as WAVE complex, activator of Arp2/3 complex at the lamellipodial tip

. Thus, Arpin is involved in so called «incoherent feed-forward loop» that is formed by two antagonistic pathways: activating Rac-WAVE complex-Arp2/3 complex and inactivating Rac-Arpin-Arp2/3 complex

, In my thesis we showed that Arpin has two binding partners -Tankyrase-1 and Tankyrase

S. Smith, ADP-ribose)polymerase (PARP) family proteins that are localized to the telomeres and bind telomeric DNA-binding proteins TRF1 and TRF2, while TRF2 is known to protect telomere ends, and TRF1 negatively regulates the length of telomeres, Tankyrases are the poly

, Tankyrase has two homologs: 142 kDa Tankyrase-1 (TNKS1) and 130 kDa Tankyrase

S. Smith, TNKS1 and TNKS2 share 85% amino acid identity and they are supposed to have the same functions, 1998.

, Tankyrases interact with a wide spectrum of proteins and mediate poly(ADP-ribosyl)ation of these proteins thus regulating essential cellular processes. Tankyrases bind telomeres, centrosomes, Golgi apparatus, NuMA (nuclear mitotic apparatus protein), SH3BP2 and others 2. First full-length three-dimensional structure of Tankyrase-1 and Tankyrase-2 bound to Arpin Tankyrase-1 consists of N-terminal histidine-, proline-, serine-rich (HPS) domain, five ankyrin repeat clusters (ARCs domain), However, unlikely Tankyrase-1, over expression of Tankyrase-2 caused a rapid cell death

, I'd like to thank the Embassy of France in Moscow for the Vernadski scholarship that allowed me to arrive in the lab of Pr

, I'm grateful to both supervisors of my thesis Pr. Alexis Gautreau and Pr. Olga Sokolova for their support during this joint PhD

. Pr, Alexis Gautreau invited me in his lab as a PhD student and he always helped me with

, Alexis Gautreau without any practice of molecular biology techniques and I'm thankful to all the team members Anna Polesskaya, Stéphane Romero, Nathalie Rocques, Nicolas Molinie and Artem Fokin for their guidance, support and helpful recommendations. Special mentioning -Sai Prasanna Visweshwaran, lab of Pr

, I would like to thank all the members of BIOC laboratory for their generous assistance with my project

, I'm really grateful to the Structural Biotechnology Group in Moscow and especially to my

. O. Russian-supervisor-pr and . Sokolova, She gave me an idea of this joint PhD with Pr. Alexis Gautreau and she supported me with all the documentation work and administrative issues

, Olga Sokolova has being my supervisor since my baccalaureate and all this time she has being teaching, influencing and supporting me. I'd like to thank Maria Karlova and Grigory Gluhov from the Structural Biotechnology Group for their helpful recommendations

, Last, but not least, I'm thankful to the Russian Science Foundation for material support of my work in Moscow, pp.14-14