000096127 001__ 96127
000096127 005__ 20210902121900.0
000096127 0247_ $$2doi$$a10.3390/ijms21197428
000096127 0248_ $$2sideral$$a120707
000096127 037__ $$aART-2020-120707
000096127 041__ $$aeng
000096127 100__ $$0(orcid)0000-0003-0668-977X$$aNeira, J.L.$$uUniversidad de Zaragoza
000096127 245__ $$aThe paralogue of the intrinsically disordered nuclear protein 1 has a nuclear localization sequence that binds to human importin a3
000096127 260__ $$c2020
000096127 5060_ $$aAccess copy available to the general public$$fUnrestricted
000096127 5203_ $$aNumerous carrier proteins intervene in protein transport from the cytoplasm to the nucleus in eukaryotic cells. One of those is importin a, with several human isoforms; among them, importin a3 (Impa3) features a particularly high flexibility. The protein NUPR1L is an intrinsically disordered protein (IDP), evolved as a paralogue of nuclear protein 1 (NUPR1), which is involved in chromatin remodeling and DNA repair. It is predicted that NUPR1L has a nuclear localization sequence (NLS) from residues Arg51 to Gln74, in order to allow for nuclear translocation. We studied in this work the ability of intact NUPR1L to bind Impa3 and its depleted species, ¿Impa3, without the importin binding domain (IBB), using fluorescence, isothermal titration calorimetry (ITC), circular dichroism (CD), nuclear magnetic resonance (NMR), and molecular docking techniques. Furthermore, the binding of the peptide matching the isolated NLS region of NUPR1L (NLS-NUPR1L) was also studied using the same methods. Our results show that NUPR1L was bound to Imp a3 with a low micromolar affinity (~5 µM). Furthermore, a similar affinity value was observed for the binding of NLS-NUPR1L. These findings indicate that the NLS region, which was unfolded in isolation in solution, was essentially responsible for the binding of NUPR1L to both importin species. This result was also confirmed by our in silico modeling. The binding reaction of NLS-NUPR1L to ¿Impa3 showed a larger affinity (i.e., lower dissociation constant) compared with that of Impa3, confirming that the IBB could act as an auto-inhibition region of Impa3. Taken together, our findings pinpoint the theoretical predictions of the NLS region in NUPR1L and, more importantly, suggest that this IDP relies on an importin for its nuclear translocation.
000096127 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B25-17R$$9info:eu-repo/grantAgreement/ES/DGA/E45-17R$$9info:eu-repo/grantAgreement/ES/ISCIII/CIBERehd$$9info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BFU2016-78232-P$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/RTI2018-097991-B-I00
000096127 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000096127 590__ $$a5.923$$b2020
000096127 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b67 / 297 = 0.226$$c2020$$dQ1$$eT1
000096127 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b49 / 178 = 0.275$$c2020$$dQ2$$eT1
000096127 592__ $$a1.455$$b2020
000096127 593__ $$aCatalysis$$c2020$$dQ1
000096127 593__ $$aComputer Science Applications$$c2020$$dQ1
000096127 593__ $$aInorganic Chemistry$$c2020$$dQ1
000096127 593__ $$aSpectroscopy$$c2020$$dQ1
000096127 593__ $$aMolecular Biology$$c2020$$dQ1
000096127 593__ $$aOrganic Chemistry$$c2020$$dQ1
000096127 593__ $$aPhysical and Theoretical Chemistry$$c2020$$dQ1
000096127 593__ $$aMedicine (miscellaneous)$$c2020$$dQ1
000096127 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000096127 700__ $$aRizzuti, B.
000096127 700__ $$0(orcid)0000-0003-4726-7821$$aJiménez-Alesanco, A.$$uUniversidad de Zaragoza
000096127 700__ $$0(orcid)0000-0001-5664-1729$$aAbián, O.$$uUniversidad de Zaragoza
000096127 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza
000096127 700__ $$aIovanna, J.L.
000096127 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000096127 7102_ $$15007$$2570$$aUniversidad de Zaragoza$$bDpto. Informát.Ingenie.Sistms.$$cÁrea Lenguajes y Sistemas Inf.
000096127 773__ $$g21, 19 (2020), 7428 [19 pp]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000096127 8564_ $$s754203$$uhttps://zaguan.unizar.es/record/96127/files/texto_completo.pdf$$yVersión publicada
000096127 8564_ $$s509144$$uhttps://zaguan.unizar.es/record/96127/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000096127 909CO $$ooai:zaguan.unizar.es:96127$$particulos$$pdriver
000096127 951__ $$a2021-09-02-10:35:03
000096127 980__ $$aARTICLE