Partner-Mediated Polymorphism of an Intrinsically Disordered Protein
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| Název: | Partner-Mediated Polymorphism of an Intrinsically Disordered Protein |
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| Autoři: | Bignon, Christophe, Troilo, Francesca, Gianni, Stefano, Longhi, Sonia |
| Přispěvatelé: | Architecture et fonction des macromolécules biologiques (AFMB), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Department of Biochemical Sciences "Rossi Fanelli", Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma "La Sapienza" = Sapienza University Rome, This work was supported by the CNRS. It was also partly supported by the European program H2020 under the EVAg Research Infrastructure (grant agreement 653316). F.T. is a recipient of a PhD fellowship from the Italo-French University. |
| Zdroj: | ISSN: 0022-2836. |
| Informace o vydavateli: | HAL CCSD Elsevier |
| Rok vydání: | 2018 |
| Sbírka: | Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
| Témata: | N(TAIL), XD, induced folding, major inducible heat shock protein (hsp70), measles virus, MESH: Amino Acid Substitution, MESH: Binding Sites, MESH: Viral Proteins/metabolism, MESH: HSP70 Heat-Shock Proteins/metabolism, MESH: Intrinsically Disordered Proteins/chemistry, MESH: Intrinsically Disordered Proteins/genetics, MESH: Intrinsically Disordered Proteins/metabolism, MESH: Measles virus/genetics, MESH: Measles virus/metabolism, MESH: Models, Molecular, MESH: Nucleoproteins/chemistry, MESH: Nucleoproteins/genetics, MESH: Nucleoproteins/metabolism, MESH: Phosphoproteins/metabolism, MESH: Protein Binding, MESH: Protein Conformation, alpha-Helical, MESH: Protein Folding, MESH: Viral Proteins/chemistry, MESH: Viral Proteins/genetics, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] |
| Popis: | International audience ; Intrinsically disordered proteins (IDPs) recognize their partners through molecular recognition elements (MoREs). The MoRE of the C-terminal intrinsically disordered domain of the measles virus nucleoprotein (NTAIL) is partly pre-configured as an α-helix in the free form and undergoes α-helical folding upon binding to the X domain (XD) of the viral phosphoprotein. Beyond XD, NTAIL also binds the major inducible heat shock protein 70 (hsp70). So far, no structural information is available for the NTAIL/hsp70 complex. Using mutational studies combined with a protein complementation assay based on green fluorescent protein reconstitution, we have investigated both NTAIL/XD and NTAIL/hsp70 interactions. Although the same NTAIL region binds the two partners, the binding mechanisms are different. Hsp70 binding is much more tolerant of MoRE substitutions than XD, and the majority of substitutions lead to an increased NTAIL/hsp70 interaction strength. Furthermore, while an increased and a decreased α-helicity of the MoRE lead to enhanced and reduced interaction strength with XD, respectively, the impact on hsp70 binding is negligible, suggesting that the MoRE does not adopt an α-helical conformation once bound to hsp70. Here, by showing that the α-helical conformation sampled by the free form of the MoRE does not systematically commit it to adopt an α-helical conformation in the bound form, we provide an example of partner-mediated polymorphism of an IDP and of the relative insensitiveness of the bound structure to the pre-recognition state. The present results therefore contribute to shed light on the molecular mechanisms by which IDPs recognize different partners. |
| Druh dokumentu: | article in journal/newspaper |
| Jazyk: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/29197511; hal-01802951; https://hal.archives-ouvertes.fr/hal-01802951; PUBMED: 29197511 |
| DOI: | 10.1016/j.jmb.2017.11.012 |
| Dostupnost: | https://hal.archives-ouvertes.fr/hal-01802951 https://doi.org/10.1016/j.jmb.2017.11.012 |
| Přístupové číslo: | edsbas.9F765558 |
| Databáze: | BASE |
Nájsť tento článok vo Web of Science | Abstrakt: | International audience ; Intrinsically disordered proteins (IDPs) recognize their partners through molecular recognition elements (MoREs). The MoRE of the C-terminal intrinsically disordered domain of the measles virus nucleoprotein (NTAIL) is partly pre-configured as an α-helix in the free form and undergoes α-helical folding upon binding to the X domain (XD) of the viral phosphoprotein. Beyond XD, NTAIL also binds the major inducible heat shock protein 70 (hsp70). So far, no structural information is available for the NTAIL/hsp70 complex. Using mutational studies combined with a protein complementation assay based on green fluorescent protein reconstitution, we have investigated both NTAIL/XD and NTAIL/hsp70 interactions. Although the same NTAIL region binds the two partners, the binding mechanisms are different. Hsp70 binding is much more tolerant of MoRE substitutions than XD, and the majority of substitutions lead to an increased NTAIL/hsp70 interaction strength. Furthermore, while an increased and a decreased α-helicity of the MoRE lead to enhanced and reduced interaction strength with XD, respectively, the impact on hsp70 binding is negligible, suggesting that the MoRE does not adopt an α-helical conformation once bound to hsp70. Here, by showing that the α-helical conformation sampled by the free form of the MoRE does not systematically commit it to adopt an α-helical conformation in the bound form, we provide an example of partner-mediated polymorphism of an IDP and of the relative insensitiveness of the bound structure to the pre-recognition state. The present results therefore contribute to shed light on the molecular mechanisms by which IDPs recognize different partners. |
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| DOI: | 10.1016/j.jmb.2017.11.012 |