Specific loop modifications of the thrombin-binding aptamer trigger the formation of parallel structures

Guanine-rich sequences show large structural variability, with folds ranging from duplex to triplex and quadruplex helices. Quadruplexes are polymorphic, and can show multiple stoichiometries, parallel and antiparallel strand alignments, and different topological arrangements. We analyze here the eq...

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Autores: Aviñó, Anna, Portella, Guillem, Ferreira, Rubén, Gargallo, Raimundo, Mazzini, Stefania, Gabelica, Valérie, Orozco, Modesto, Eritja Casadellà, Ramón
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2014
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/126488
Acceso en línea:http://hdl.handle.net/10261/126488
Access Level:acceso abierto
Palabra clave:DNA polymorphism
G-quadruplex
nucleic acid structure
thermal stability
thrombin-binding aptamer
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spelling Specific loop modifications of the thrombin-binding aptamer trigger the formation of parallel structures Aviñó, Anna Portella, Guillem Ferreira, Rubén Gargallo, Raimundo Mazzini, Stefania Gabelica, Valérie Orozco, Modesto Eritja Casadellà, Ramón DNA polymorphism G-quadruplex nucleic acid structure thermal stability thrombin-binding aptamer Guanine-rich sequences show large structural variability, with folds ranging from duplex to triplex and quadruplex helices. Quadruplexes are polymorphic, and can show multiple stoichiometries, parallel and antiparallel strand alignments, and different topological arrangements. We analyze here the equilibrium between intramolecular antiparallel and intermolecular parallel G-quadruplexes in the thrombin-binding aptamer (TBA) sequence. Our theoretical and experimental studies demonstrate that an apparently simple modification at the loops of TBA induces a large change in the monomeric antiparallel structure of TBA to yield a parallel G-quadruplex showing a novel T-tetrad. The present results illustrate the extreme polymorphism of G-quadruplexes and the ease with which their conformation in solution can be manipulated by nucleotide modification. This work was supported by the Spanish Ministry of Science and Innovation, MICINN (CTQ2010-20541, CTQ2012-38616, BIO2009-10964 and Consolider E-Science), the Generalitat de Catalunya, (2009/SGR/208), the University of Milano (PUR 2009 Funds), the funds de la Recherche ScientifiqueFNRS (VG research associate position and FRFC grant 2.4528.11) and PRIN09 (2009Prot- 2009J54YAP_005). RF is a recipient of a FPI predoctoral contract (MICINN) and a STSM from COST (G4net, MP0802). GP is a recipient of a Sara Borrell postdoctoral fellowship. Collaborative research was funded by a Cost action (G4net, MP0802) and an Italian-Spanish collaborative action (IT2009-0067). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. Peer reviewed Wiley-Blackwell http://hdl.handle.net/10261/126488
title Specific loop modifications of the thrombin-binding aptamer trigger the formation of parallel structures
spellingShingle Specific loop modifications of the thrombin-binding aptamer trigger the formation of parallel structures
Aviñó, Anna
DNA polymorphism
G-quadruplex
nucleic acid structure
thermal stability
thrombin-binding aptamer
title_short Specific loop modifications of the thrombin-binding aptamer trigger the formation of parallel structures
title_full Specific loop modifications of the thrombin-binding aptamer trigger the formation of parallel structures
title_fullStr Specific loop modifications of the thrombin-binding aptamer trigger the formation of parallel structures
title_full_unstemmed Specific loop modifications of the thrombin-binding aptamer trigger the formation of parallel structures
title_sort Specific loop modifications of the thrombin-binding aptamer trigger the formation of parallel structures
author Aviñó, Anna
author_facet Aviñó, Anna
Portella, Guillem
Ferreira, Rubén
Gargallo, Raimundo
Mazzini, Stefania
Gabelica, Valérie
Orozco, Modesto
Eritja Casadellà, Ramón
author_role author
author2 Portella, Guillem
Ferreira, Rubén
Gargallo, Raimundo
Mazzini, Stefania
Gabelica, Valérie
Orozco, Modesto
Eritja Casadellà, Ramón
author2_role author
author
author
author
author
author
author
topic DNA polymorphism
G-quadruplex
nucleic acid structure
thermal stability
thrombin-binding aptamer
topic_facet DNA polymorphism
G-quadruplex
nucleic acid structure
thermal stability
thrombin-binding aptamer
description Guanine-rich sequences show large structural variability, with folds ranging from duplex to triplex and quadruplex helices. Quadruplexes are polymorphic, and can show multiple stoichiometries, parallel and antiparallel strand alignments, and different topological arrangements. We analyze here the equilibrium between intramolecular antiparallel and intermolecular parallel G-quadruplexes in the thrombin-binding aptamer (TBA) sequence. Our theoretical and experimental studies demonstrate that an apparently simple modification at the loops of TBA induces a large change in the monomeric antiparallel structure of TBA to yield a parallel G-quadruplex showing a novel T-tetrad. The present results illustrate the extreme polymorphism of G-quadruplexes and the ease with which their conformation in solution can be manipulated by nucleotide modification.
publishDate 2014
format article
status_str acceptedVersion
url http://hdl.handle.net/10261/126488
eu_rights_str_mv openAccess
publisher Wiley-Blackwell
institution Consejo Superior de Investigaciones Científicas (CSIC)
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
_version_ 1878434479612100609
publishDateSort 2014
author_browse Aviñó, Anna
Eritja Casadellà, Ramón
Ferreira, Rubén
Gabelica, Valérie
Gargallo, Raimundo
Mazzini, Stefania
Orozco, Modesto
Portella, Guillem
publisherStr Wiley-Blackwell
score 6,9303427

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