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http://hdl.handle.net/2445/140129
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DC Field | Value | Language |
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dc.contributor.author | Wang, Yong Jian | - |
dc.contributor.author | Rico-Lastres, Palma | - |
dc.contributor.author | Lezamiz, Ainhoa | - |
dc.contributor.author | Mora, Marc | - |
dc.contributor.author | Solsona Sancho, Carles | - |
dc.contributor.author | Stirnemann, Guillaume | - |
dc.contributor.author | Garcia-Manyes, Sergi | - |
dc.date.accessioned | 2019-09-16T17:51:13Z | - |
dc.date.available | 2019-09-16T17:51:13Z | - |
dc.date.issued | 2018-06-20 | - |
dc.identifier.issn | 1948-7185 | - |
dc.identifier.uri | http://hdl.handle.net/2445/140129 | - |
dc.description.abstract | Understanding the molecular mechanisms governing protein-nucleic acid interactions is fundamental to many nuclear processes. However, how nucleic acid binding affects the conformation and dynamics of the substrate protein remains poorly understood. Here we use a combination of single molecule force spectroscopy AFM and biochemical assays to show that the binding of TG-rich ssDNA triggers a mechanical switch in the RRM1 domain of TDP-43, toggling between an entropic spring devoid of mechanical stability and a shock absorber bound-form that resists unfolding forces of ∼40 pN. The fraction of mechanically resistant proteins correlates with an increasing length of the TGn oligonucleotide, demonstrating that protein mechanical stability is a direct reporter of nucleic acid binding. Steered molecular dynamics simulations on related RNA oligonucleotides reveal that the increased mechanical stability fingerprinting the holo-form is likely to stem from a unique scenario whereby the nucleic acid acts as a 'mechanical staple' that protects RRM1 from mechanical unfolding. Our approach highlights nucleic acid binding as an effective strategy to control protein nanomechanics. | - |
dc.format.extent | 8 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Chemical Society | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1021/acs.jpclett.8b01494 | - |
dc.relation.ispartof | Journal of Physical Chemistry Letters, 2018, vol. 9, num. 14, p. 3800-3807 | - |
dc.relation.uri | https://doi.org/10.1021/acs.jpclett.8b01494 | - |
dc.rights | (c) American Chemical Society , 2018 | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | ADN | - |
dc.subject.classification | Química | - |
dc.subject.classification | Gens | - |
dc.subject.classification | Proteïnes supressores de tumors | - |
dc.subject.other | DNA | - |
dc.subject.other | Chemistry | - |
dc.subject.other | Genes | - |
dc.subject.other | Tumor suppressor protein | - |
dc.title | DNA binding induces a nanomechanical switch in the RRM1 domain of TDP-43 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 689268 | - |
dc.date.updated | 2019-09-16T17:51:13Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/731957/EU//MECHANO-CONTROL | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 29924934 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Articles publicats en revistes (Patologia i Terapèutica Experimental) |
Files in This Item:
File | Description | Size | Format | |
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689268.pdf | 969.07 kB | Adobe PDF | View/Open |
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