Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding partners

Pankaj Sharma, Elena Maklashina, Markus Voehler, Sona Balintova, Sarka Dvorakova, Michal Kraus, Katerina Hadrava Vanova, Zuzana Nahacka, Renata Zobalova, Stepana Boukalova, Kristyna Cunatova, Tomas Mracek, Hans K. Ghayee, Karel Pacak, Jakub Rohlena, Jiri Neuzil (), Gary Cecchini () and T. M. Iverson ()
Additional contact information
Pankaj Sharma: Vanderbilt University
Elena Maklashina: San Francisco VA Health Care System
Markus Voehler: Department of Chemistry Vanderbilt University
Sona Balintova: Czech Academy of Sciences
Sarka Dvorakova: Czech Academy of Sciences
Michal Kraus: Czech Academy of Sciences
Katerina Hadrava Vanova: Czech Academy of Sciences
Zuzana Nahacka: Czech Academy of Sciences
Renata Zobalova: Czech Academy of Sciences
Stepana Boukalova: Czech Academy of Sciences
Kristyna Cunatova: Czech Academy of Sciences
Tomas Mracek: Czech Academy of Sciences
Hans K. Ghayee: University of Florida College of Medicine and Malcom Randall, VA Medical Center
Karel Pacak: National Institutes of Health
Jakub Rohlena: Czech Academy of Sciences
Jiri Neuzil: Czech Academy of Sciences
Gary Cecchini: San Francisco VA Health Care System
T. M. Iverson: Vanderbilt University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-023-44563-7

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