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Tubulin is able to switch between a straight microtubule-like structure and a curved structure in complex with the stathmin-like domain of the RB3 protein (T(2)RB3). GTP hydrolysis following microtubule assembly induces protofilament curvature and disassembly. The conformation of the labile tubulin heterodimers is unknown. One important question is whether free GDP-tubulin dimers are straightened by GTP binding or if GTP-tubulin is also curved and switches into a straight conformation upon assembly. We have obtained insight into the bending flexibility of tubulin by analyzing the interplay of tubulin-stathmin association with the binding of several small molecule inhibitors to the colchicine domain at the tubulin intradimer interface, combining structural and biochemical approaches. The crystal structures of T(2)RB3 complexes with the chiral R and S isomers of ethyl-5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl-carbamate, show that their binding site overlaps with colchicine ring A and that both complexes have the same curvature as unliganded T(2)RB3. The binding of these ligands is incompatible with a straight tubulin structure in microtubules. Analytical ultracentrifugation and binding measurements show that tubulin-stathmin associations (T(2)RB3, T(2)Stath) and binding of ligands (R, S, TN-16, or the colchicine analogue MTC) are thermodynamically independent from one another, irrespective of tubulin being bound to GTP or GDP. The fact that the interfacial ligands bind equally well to tubulin dimers or stathmin complexes supports a bent conformation of the free tubulin dimers. It is tempting to speculate that stathmin evolved to recognize curved structures in unassembled and disassembling tubulin, thus regulating microtubule assembly., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Tubulin is able to switch between a straight microtubule-like structure and a curved structure in complex with the stathmin-like domain of the RB3 protein (T(2)RB3). GTP hydrolysis following microtubule assembly induces protofilament curvature and disassembly. The conformation of the labile tubulin heterodimers is unknown. One important question is whether free GDP-tubulin dimers are straightened by GTP binding or if GTP-tubulin is also curved and switches into a straight conformation upon assembly. We have obtained insight into the bending flexibility of tubulin by analyzing the interplay of tubulin-stathmin association with the binding of several small molecule inhibitors to the colchicine domain at the tubulin intradimer interface, combining structural and biochemical approaches. The crystal structures of T(2)RB3 complexes with the chiral R and S isomers of ethyl-5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl-carbamate, show that their binding site overlaps with colchicine ring A and that both complexes have the same curvature as unliganded T(2)RB3. The binding of these ligands is incompatible with a straight tubulin structure in microtubules. Analytical ultracentrifugation and binding measurements show that tubulin-stathmin associations (T(2)RB3, T(2)Stath) and binding of ligands (R, S, TN-16, or the colchicine analogue MTC) are thermodynamically independent from one another, irrespective of tubulin being bound to GTP or GDP. The fact that the interfacial ligands bind equally well to tubulin dimers or stathmin complexes supports a bent conformation of the free tubulin dimers. It is tempting to speculate that stathmin evolved to recognize curved structures in unassembled and disassembling tubulin, thus regulating microtubule assembly., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Tubulin is able to switch between a straight microtubule-like structure and a curved structure in complex with the stathmin-like domain of the RB3 protein (T(2)RB3). GTP hydrolysis following microtubule assembly induces protofilament curvature and disassembly. The conformation of the labile tubulin heterodimers is unknown. One important question is whether free GDP-tubulin dimers are straightened by GTP binding or if GTP-tubulin is also curved and switches into a straight conformation upon assembly. We have obtained insight into the bending flexibility of tubulin by analyzing the interplay of tubulin-stathmin association with the binding of several small molecule inhibitors to the colchicine domain at the tubulin intradimer interface, combining structural and biochemical approaches. The crystal structures of T(2)RB3 complexes with the chiral R and S isomers of ethyl-5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl-carbamate, show that their binding site overlaps with colchicine ring A and that both complexes have the same curvature as unliganded T(2)RB3. The binding of these ligands is incompatible with a straight tubulin structure in microtubules. Analytical ultracentrifugation and binding measurements show that tubulin-stathmin associations (T(2)RB3, T(2)Stath) and binding of ligands (R, S, TN-16, or the colchicine analogue MTC) are thermodynamically independent from one another, irrespective of tubulin being bound to GTP or GDP. The fact that the interfacial ligands bind equally well to tubulin dimers or stathmin complexes supports a bent conformation of the free tubulin dimers. It is tempting to speculate that stathmin evolved to recognize curved structures in unassembled and disassembling tubulin, thus regulating microtubule assembly.

Numérisation effectuée à partir d'un document original., Appartient à l'ensemble documentaire : RegiaCharlesV, Charles V (1338-1380 ; roi de France)., Jean (1389-1435 ; duc de Bedford)., Humphrey (1391-1447 ; duc de Gloucester)., Dorléans, Louis (1542-1629)., Couvent des Minimes de Nigeon (Paris). Bibliothèque.

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Avec mode texte, Poésie française -- +* 1500......- 1599......+:16e siècle, Ouvrages avant 1800

Comprend : Relation de la mort de MM. les duc et cardinal de Guise... 1588 ; Le Procez-verbal d'un nommé Nicolas Poulain,... qui contient l'histoire de la Ligue, depuis le second janvier 1585 jusques au jour des Barricades, escheues le 12 may 1588 ; La saincte et très chrestienne Résolution de Monseigneur l'illustrissime... Cardinal de Bourbon, pour maintenir l'Eglise catholique et romaine... Par F. I. B. Parisien... ; Lettre... contenant brève réponse aux calomnies d'un certain prétendu anglais... 1586 ; Déclaration... à l'encontre de Henri de Bourbon, soi-disant roi de Navarre, et Henri semblablement de Bourbon, prétendu prince de Condé, hérétiques... ; Advertissement des catholiques anglois aux François catholiques, du danger où ils sont de perdre leur religion ; Coppie d'une lettre escrite au Roy et extraict d'une autre aux princes et seigneurs françois, le 17. jour de may dernier, par Mgr le duc de Guise,... ; Les propos que le roy a tenuz à Chartres aux deputez de sa Cour de Parlement de Paris ; Copie de l'Opposition faite par le roi de Navarre et Mgr le prince de Condé, contre l'excommunication du pape Sixte V... (affiché à Rome le 6 nov. 1585), Contient une table des matières

Poésie française -- +* 1500......- 1599......+:16e siècle, Ouvrages avant 1800

Contient une table des matières, Ouvrages avant 1800

Collection : French books before 1601 ; 452.4

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