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| Item Type: | Preprint |
|---|---|
| Title: | Structural studies suggest CCDC127 as a novel membrane contact site protein in the mitochondrial intermembrane space |
| Creators Name: | Bock-Bierbaum, Tobias, von der Malsburg, Karina, Natarajan, Ashwin Karthick, Zarges, Christine, Akkaya, Kerem Can, Aladawi, Amjad, Noll, Katja, Jungbluth, Sibylle, Schirra, Claudia, Zhu, Ying, Cremer, Nils, Bernert, Carola, Liu, Fan, Lehmann, Martin, Riemer, Jan, van der Laan, Martin and Daumke, Oliver |
| Abstract: | Mitochondria feature a sophisticated membrane architecture, with a planar mitochondrial outer membrane (MOM) and a folded inner membrane (MIM). Due to the remarkable adaptability of mitochondria, a proteinaceous network in the intermembrane space (IMS) was proposed to confer both stability and flexibility. However, components of such scaffolds, tentatively termed the ’mitoskeleton’, have remained largely elusive. The mitochondrial contact site and organizing system (MICOS), a central organizer of mitochondrial membrane architecture, was suggested to participate in ’mitoskeleton’ formation. Here, we structurally characterize the coiled-coil domain-containing 127 (CCDC127) protein, a putative interactor of MICOS. We show that CCDC127’s amino-terminal transmembrane region is anchored in the MOM and the bulk soluble part exposed to the IMS. A crystal structure of CCDC127’s central coiled-coil displays a parallel dimer which further oligomerizes into tetramers. We demonstrate that the carboxy-terminal helical bundle (CHB) domain dimerizes to create a peripheral membrane-binding site. Supported by electron microscopy data, we propose a structural model of CCDC127 as intramitochondrial membrane contact site protein mediating the structural organization of the IMS as part of the ’mitoskeleton’. |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2025.12.11.693622 |
| Date: | 16 December 2025 |
| Additional Information: | Accession "9REU" is on HOLD, meaning: processing complete, entry on hold until a certain date. |
| Official Publication: | https://doi.org/10.64898/2025.12.11.693622 |
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