Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding partners
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Maklashina, Elena
Voehler, Markus
Balintova, Sona
Dvorakova, Sarka
Kraus, Michal
Vanova, Katerina Hadrava
Nahacka, Zuzana
Zobalova, Renata
Boukalova, Stepana
Cunatova, Kristyna
Mracek, Tomas
Ghayee, Hans K
Pacak, Karel
Rohlena, Jakub
et al.
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Abstract
Complex II (CII) activity controls phenomena that require crosstalk between metabolism and signaling, including neurodegeneration, cancer metabolism, immune activation, and ischemia-reperfusion injury. CII activity can be regulated at the level of assembly, a process that leverages metastable assembly intermediates. The nature of these intermediates and how CII subunits transfer between metastable complexes remains unclear. In this work, we identify metastable species containing the SDHA subunit and its assembly factors, and we assign a preferred temporal sequence of appearance of these species during CII assembly. Structures of two species show that the assembly factors undergo disordered-to-ordered transitions without the appearance of significant secondary structure. The findings identify that intrinsically disordered regions are critical in regulating CII assembly, an observation that has implications for the control of assembly in other biomolecular complexes.
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Nature Communications
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15
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© The Author(s) 2024, corrected publication 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Biomedical and clinical sciences
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Sharma, P; Maklashina, E; Voehler, M; Balintova, S; Dvorakova, S; Kraus, M; Vanova, KH; Nahacka, Z; Zobalova, R; Boukalova, S; Cunatova, K; Mracek, T; Ghayee, HK; Pacak, K; Rohlena, J; et al., Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding partners, Nature Communications, 2024, 15, pp. 473