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

Nat Commun. 2024-01; 
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,T M Iverson
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Gene Synthesis The DNA sequence encoding the mature SDHAF4 protein (amino acid residues 20–108) was optimized for E. coli expression, synthesized (Genscript), and cloned into the 5′ BamHI and 3′KpnI fragment of pST50Trc3-FLAG (Addgene57) Get A Quote

摘要

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 transition... More

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