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Structural Studies of the Staphylococcus Aureus Ribosome Iskander Khusainov

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Structural Studies of the Staphylococcus Aureus Ribosome Iskander Khusainov Structural studies of the Staphylococcus aureus ribosome Iskander Khusainov To cite this version: Iskander Khusainov. Structural studies of the Staphylococcus aureus ribosome. Biophysics. Université de Strasbourg, 2015. English. NNT : 2015STRAJ071. tel-01403855 HAL Id: tel-01403855 https://tel.archives-ouvertes.fr/tel-01403855 Submitted on 28 Nov 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ DE STRASBOURG ÉCOLE DOCTORALE des Sciences de la Vie et de la Santé IGBMC - CNRS UMR 7104 - Inserm U 964 THÈSE présentée par : Iskander KHUSAINOV soutenue le : 27 Novembre 2015 pour obtenir le grade de : !"#$%&'($')R%+,-$&.,# '($'0#&1.2!%&3 Discipline/ Spécialité : Biophysique et biologie structurale (Biophysics and Structural biology) Structural studies of the Staphylococcus aureus ribosome Etudes structurales du ribosome de Staphylococcus aureus THÈSE dirigée par : M. YUSUPOV Marat Directeur de recherche, Université de Strasbourg Mme. YUSUPOVA Gulnara Directeur de recherche, Université de Strasbourg RAPPORTEURS : M. JENNER Lasse B. Associate Professor, Aarhus University (Denmark) M. MECHULAM Yves Directeur de recherche, École Polytechnique (Paris) AUTRES MEMBRES DU JURY : M. GEISSMANN Thomas Chargé de recherches, ENS de Lyon (Lyon) M. MARZI Stefano Chargé de recherches, Université de Strasbourg AcknowledgementsAcknowled ge ments ACKNOWLEDGEMENTS F1`s Q` :CC : 1Q%CR C1@V Q .:J@ :CC =%`7 IVIGV`s5 D`8 0Vs MVH.%C:I5 D`8 L:ssV BQ.C JVJJV`5 D`8 T.QI:s GV1ssI:JJ :JR D`8 S V`:JQ M:`<1 1.Q :$`VVR Q V0:C%: V I7 P.D 1Q`@8 I :I V6 `VIVC7 .:J@`%C Q IVV .VI 1J S `:sGQ%`$ :JR Q R1sH%ss8 I 1Q%CR C1@V Q V6]`Vss I7 s1JHV`V $`: 1 %RV Q I7 :R01sQ`s5 G%C: :JR M:`: `Q` .V1` HQJs :J s%]]Q` :JR ]: 1VJHV5 `Q` .V1` IQ 10: 1QJ5 :R01HV :JR HQJ`1RVJHV8 I :I .:J@`%C Q .VI `Q` $101J$ IV .V Q]]Q` %J1 7 Q CV:`J I:J7 R1``V`VJ Q` IV .QRs Q` G1QH.VI1s `7 :JR s `%H %`:C :J:C7s1s 1J .V C:GQ`: Q`78 E0V`7 s1J$CV R:7 I CV:`J sQIV .1J$ JV1 .V`V8 Q`@1J$ 1J M:`: s :JR G%C:s C:GQ`: Q`1Vs 1s ]`1HVCVss V6]V`1VJHV8 T.1s 1Q`@ 1Q%CR JQ GV HQI]CV V 11 .Q% VCVH `QJ I1H`QsHQ]7 1J0QC0VIVJ 8 I V6]`Vss I7 $`: 1 %RV Q Q%` HQCC:GQ`: Q` :sV` H:s.VI 11 . 1.QI 1V QG :1JVR .V `1`s s `%H %`V Q` S :]. `1GQsQIV6 :JR Q ACV6 M7:sJ1@Q0 `Q` .1s s1$J1`1H:J HQJ `1G% 1QJ 1J H`7QREM R: : HQCCVH 1QJ :JR .VC]`%C R1sH%ss1QJs8 S]VH1:C `V$:`Rs Q D`8 P:sH:CV RQIG78 I 1s :C1:7s : ]CV:s%`V Q R1sH%ss 11 . .V` :JR Q $V : ``Vs. 01V1 QJ .V ]`Q=VH 8 I :I .:J@`%C Q .V s `%H %`:C G1QCQ$7 ]C: `Q`I Q` IGBMC7 C: .V`1JV5 PV1``V :JR AC:s :1`5 1.Q :%$. IV : CQ Q` VH.J1_%Vs Q` G1Q].7s1Hs :JR H`7s :CC1<: 1QJ8 IJ :RR1 1QJ5 I .:J@ P`Q`8 R1H.:`R BVH@V :JR D`8 F:`1R: M1J1G:7V0: `Q` ]: 1VJ C7 HQ``VH 1J$ I7 .Vs1s :JR G`1J$1J$ 1 Q 1 s ]`VsVJ :GCV `Q`I8 NQ1 1 1s : $QQR 1IV Q .:J@ :CC Q` I7 HQCCV:$%Vs 1.Q I:RV IV `VVC HQI`Q` :GCV .V`V8 F1`s 5 I 1:J Q HQ`R1:CC7 .:J@ 1Q ]VQ]CV7 SV`$V75 1.QsV VJRCVss VJ .%s1:sI :JR s `1@1J$ V`%R1 1QJ 1Js]1`VR IV Q IQ0V `Q`1:`R ``QI R:7 Q R:76 :JR N: :s.:5 1.Q .VC]VR IV Q JQ $V CQs 1J .V `1GQsQIV 1Q`CR R%`1J$ I7 `1`s 7V:`8 G`:H1:sLG`:<1V Q I7 VEF V:I ER%:`RQ :JR S1IQJV8 T.VsV 1Q ]VQ]CV ]`VsVJ :J %JGVC1V0:GCV HQIG1J: 1QJ Q` V6]V`1VJHV5 @JQ1CVR$V5 H%`1Qs1 75 R1C1$VJHV5 GVC1V` :JR `V:sQJ:GCV s@V] 1H1sI .: I:@V .VI V6 `VIVC7 J1HV HQI]:J1QJs8 AJR ]:` 1H%C:` H`VR1 s Q ACV6V7 Q` HQ%`sV8 AC1:7s s `1H 5 :C1:7s s `:1$. `Q`1:`R5 sQIV 1IVs s:`H:s 1H G% JV0V` R1s1J$VJ%Q%s5 .V I:RV Q%` s7JH.`Q `QJ `1]s 0V`7 s]VH1:C8 M:J7 .:J@s Q Q%` F`VJH. V:II: Vs J%s 1JV5 MXC:J1V5 D:01R8 T.:J@s Q .VI5 I @JV1 IQ`V :GQ% F`VJH. H%C %`V5 H%1s1JV5 :JR IQs 1I]Q` :J C75 .V7 1V`V :C1:7s .VC]`%C 11 . .V F`VJH. C:J$%:$V :JR :RI1J1s `: 1QJ R% 1Vs8 AJR I:J7 .:J@s Q :CC .V ]`VsVJ :JR `Q`IV` IVIGV`s Q` Q%` C:G5 I`1J:5 %<%`%5 M:`1V5 D:J17:5 M%I1J=QJ5 JV:JRP:%C5 R:].:[C5 N1HQ5 S7C01V5 L:ssV5 L1%RI1C:5 `Q` .V1` s%]]Q` :JR ``1VJRC7 : IQs].V`V 1J .V C:GQ`: Q`78 2 AcknowledgementsAcknowled ge ments BVs1RVs 1Q`@ 1J .V C:GQ`: Q`75 1V .:R : $`V: 1IV Q% s1RV IGBMC8 F1`s 5 I 1Q%CR C1@V Q .:J@ Q%` E:s V`J J1QJ V:I AJJ: :JR K: V8 V IV .V`V R%`1J$ .V 1J V`01V1 :JR @V] .V ``1VJRs.1] Q0V` .V 1.QCV P.D8 I :]]`VH1: V .V .Qs]1 :C1 7 Q` BVJ :JR D:I1VJ5 1.Q s.Q1VR %s S `:sGQ%`$ :JR .VC]VR 11 . 1J V$`: 1QJ 1J Q .V F`VJH. C1`V R%`1J$ `1`s 7V:`8 I :I $`: V`%C Q N1HQ :JR CC:1`V5 F1`:s :JR I`VJV5 M:`1V :JR GX`:CR5 I`1J:5 AJJ:5 K: V5 K:`1I:5 HVVJ:5 S.1C]75 ACV6V75 Q0:5 G`1$Q`75 :CV`1Q5 :015 IsI:1C5 1V7:J$ :JR Q .V`s `Q` .V %J`Q`$V :GCV IQIVJ s :JR :R0VJ %`Vs .: 1V .:R Q$V .V`7 01: `V``: : 1J J%`:5 Q]V`: 1J D1=QJ5 s@1 1J .V AC]s5 GQ:`R $:IVs : ACV6V7s ]C:HV5 H`:<7 J1$. G1@V `1] :CQJ$ .V R.1JV :JR I:J7 Q .V`s8 I 1Q%CR C1@V Q .:J@ :CC .V IVIGV`s Q` SPB :JR ]V`sQJ:CC7 M1H.VC 1.Q :C1:7s $:0V IV : .:JR 1.VJ I :s@VR8 M:J7 .:J@s Q I7 ``1VJRs 1J K:<:J R A1R:`5 I$Q`5 SV`$V7 :JR OC$:8 I 1s :C1:7s : ]CV:s%`V Q HQIV Q .V .QIV Q1J :JR IVV .VI .V`V8 MQs 1I]Q` :J C75 I 1Q%CR C1@V Q .:J@ I7 `:I1C78 I :I 0V`7 $`: V`%C Q I7 ]:`VJ s RV<VR: :JR S.:I1C 1.Q :HHV] VR I7 11s. Q HQIV Q F`:JHV 11 . %JRV`s :JR1J$8 TQ I7 :%J F:`1R:5 1.Q s.Q1VR IV .V GV:% 7 Q` sH1VJHV :JR G1QCQ$7 1.VJ I 1:s H.1CR6 :JR Q I7 $`:JRIQ .V` J:sI1J:5 1.Q ]: 1VJ C7 C1s VJs Q :CC I7 s Q`1Vs :GQ% s7JH.`Q `QJs5 R1```:H 1QJ :JR $10Vs : $QQR :R01HV 1.VJ I JVVR QJV8 I :I :CsQ $`: V`%C Q I7 G`Q .V` F:`1R :JR I7 J1VHV R%s.:J17: 11 . 1.QI 1V s]VJ : $`V: 1IV 1J S:1J RPV V`sG%`$ .1s 7V:`8 I :I 0V`7 .:]]7 Q .:0V s%H. :J :RQ`:GCV `:I1C7* M7 P.D .Vs1s .:s GVVJ ]Qss1GCV QJC7 GVH:%sV Q` HQJs :J s%]]Q` :JR ]:` 1H1]: 1QJ Q` :CC .V ]VQ]CV IVJ 1QJVR :GQ0V8 I0V JV0V` 1:C@VR :CQJV8 T.:J@ 7Q% 0V`7 I%H.* 3 Table of contents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ÉSMÉ DE THÈSE 888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 ABBREIATIONS 8888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 INTRODCTION 88888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 THE RIBOSOME 888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 CQ`V Q` .V `1GQsQIV 88888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 S]VH1`1H: 1QJs Q` G:H V`1:C :JR V%@:`7Q 1H `1GQsQIV 8888888888888888888888888888888888888888888888888888888888888888888888888888888888 P`Q V1J s7J .Vs1s 88888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 S `%H %`:C s %R1Vs Q` .V `1GQsQIV 88888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 STAPHLOCOCCS ARES 88888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 M:1J H.:`:H V`1s 1Hs Q` S8 :%`V%s 88888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 1`%CVJHV RV V`I1J:J s 8888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 S8 :%`V%s R s%]V`G%$ 888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 AJ 1G1Q 1H `Vs1s :JHV Q` S8 :%`V%s 8888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 MVH.:J1sIs Q` :J 1G1Q 1Hs :H 1QJ :JR G:H V`1:C `Vs1s :JHV8 88888888888888888888888888888888888888888888888888888888888888888888888 C%``VJ R`%$s %sVR 1J `V: IVJ Q` S8 :%`V%s R1sV:sVs 888888888888888888888888888888888888888888888888888888888888888888888888888888 S8 :%`V%s `1GQsQIV :s : :`$V `Q` JV1 :J 1G1Q 1Hs 8888888888888888888888888888888888888888888888888888888888888888888888888888888888888 TRANSLATION ELONGATION FACTORS 888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 T`:JsC: 1QJ VCQJ$: 1QJ H7HCV 888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 VEF 1s : ]Q VJ 1:C :`$V `Q` R`%$ RV0VCQ]IVJ 8888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 PROJECT OTLINE 88888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888888 RESEARCH
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