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Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway
In humans, the biosynthesis and trafficking of mitochondrial [4Fe-4S](2+) clusters is a highly coordinated process that requires a complex protein machinery. In a mitochondrial pathway among various proposed to biosynthesize nascent [4Fe-4S](2+) clusters, two [2Fe-2S](2+) clusters are converted into...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388178/ https://www.ncbi.nlm.nih.gov/pubmed/37211204 http://dx.doi.org/10.1016/j.jmb.2023.168154 |
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author | Da Vela, Stefano Saudino, Giovanni Lucarelli, Francesca Banci, Lucia Svergun, Dmitri I. Ciofi-Baffoni, Simone |
author_facet | Da Vela, Stefano Saudino, Giovanni Lucarelli, Francesca Banci, Lucia Svergun, Dmitri I. Ciofi-Baffoni, Simone |
author_sort | Da Vela, Stefano |
collection | PubMed |
description | In humans, the biosynthesis and trafficking of mitochondrial [4Fe-4S](2+) clusters is a highly coordinated process that requires a complex protein machinery. In a mitochondrial pathway among various proposed to biosynthesize nascent [4Fe-4S](2+) clusters, two [2Fe-2S](2+) clusters are converted into a [4Fe-4S](2+) cluster on a ISCA1-ISCA2 complex. Along this pathway, this cluster is then mobilized from this complex to mitochondrial apo recipient proteins with the assistance of accessory proteins. NFU1 is the accessory protein that first receives the [4Fe-4S](2+) cluster from ISCA1-ISCA2 complex. A structural view of the protein–protein recognition events occurring along the [4Fe-4S](2+) cluster trafficking as well as how the globular N-terminal and C-terminal domains of NFU1 act in such process is, however, still elusive. Here, we applied small-angle X-ray scattering coupled with on-line size-exclusion chromatography and paramagnetic NMR to disclose structural snapshots of ISCA1-, ISCA2- and NFU1-containing apo complexes as well as the coordination of [4Fe-4S](2+) cluster bound to the ISCA1-NFU1 complex, which is the terminal stable species of the [4Fe-4S](2+) cluster transfer pathway involving ISCA1-, ISCA2- and NFU1 proteins. The structural modelling of ISCA1-ISCA2, ISCA1-ISCA2-NFU1 and ISCA1-NFU1 apo complexes, here reported, reveals that the structural plasticity of NFU1 domains is crucial to drive protein partner recognition and modulate [4Fe-4S](2+) cluster transfer from the cluster-assembly site in the ISCA1-ISCA2 complex to a cluster-binding site in the ISCA1-NFU1 complex. These structures allowed us to provide a first rational for the molecular function of the N-domain of NFU1, which can act as a modulator in the [4Fe-4S](2+) cluster transfer. |
format | Online Article Text |
id | pubmed-10388178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103881782023-08-01 Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway Da Vela, Stefano Saudino, Giovanni Lucarelli, Francesca Banci, Lucia Svergun, Dmitri I. Ciofi-Baffoni, Simone J Mol Biol Research Article In humans, the biosynthesis and trafficking of mitochondrial [4Fe-4S](2+) clusters is a highly coordinated process that requires a complex protein machinery. In a mitochondrial pathway among various proposed to biosynthesize nascent [4Fe-4S](2+) clusters, two [2Fe-2S](2+) clusters are converted into a [4Fe-4S](2+) cluster on a ISCA1-ISCA2 complex. Along this pathway, this cluster is then mobilized from this complex to mitochondrial apo recipient proteins with the assistance of accessory proteins. NFU1 is the accessory protein that first receives the [4Fe-4S](2+) cluster from ISCA1-ISCA2 complex. A structural view of the protein–protein recognition events occurring along the [4Fe-4S](2+) cluster trafficking as well as how the globular N-terminal and C-terminal domains of NFU1 act in such process is, however, still elusive. Here, we applied small-angle X-ray scattering coupled with on-line size-exclusion chromatography and paramagnetic NMR to disclose structural snapshots of ISCA1-, ISCA2- and NFU1-containing apo complexes as well as the coordination of [4Fe-4S](2+) cluster bound to the ISCA1-NFU1 complex, which is the terminal stable species of the [4Fe-4S](2+) cluster transfer pathway involving ISCA1-, ISCA2- and NFU1 proteins. The structural modelling of ISCA1-ISCA2, ISCA1-ISCA2-NFU1 and ISCA1-NFU1 apo complexes, here reported, reveals that the structural plasticity of NFU1 domains is crucial to drive protein partner recognition and modulate [4Fe-4S](2+) cluster transfer from the cluster-assembly site in the ISCA1-ISCA2 complex to a cluster-binding site in the ISCA1-NFU1 complex. These structures allowed us to provide a first rational for the molecular function of the N-domain of NFU1, which can act as a modulator in the [4Fe-4S](2+) cluster transfer. Elsevier 2023-08-01 /pmc/articles/PMC10388178/ /pubmed/37211204 http://dx.doi.org/10.1016/j.jmb.2023.168154 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Da Vela, Stefano Saudino, Giovanni Lucarelli, Francesca Banci, Lucia Svergun, Dmitri I. Ciofi-Baffoni, Simone Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway |
title | Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway |
title_full | Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway |
title_fullStr | Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway |
title_full_unstemmed | Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway |
title_short | Structural Plasticity of NFU1 Upon Interaction with Binding Partners: Insights into the Mitochondrial [4Fe-4S] Cluster Pathway |
title_sort | structural plasticity of nfu1 upon interaction with binding partners: insights into the mitochondrial [4fe-4s] cluster pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388178/ https://www.ncbi.nlm.nih.gov/pubmed/37211204 http://dx.doi.org/10.1016/j.jmb.2023.168154 |
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