9OYR
Structure of D2-NT amyloid fibrils
Summary for 9OYR
| Entry DOI | 10.2210/pdb9oyr/pdb |
| EMDB information | 45976 71028 71031 71032 71033 |
| Descriptor | Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (1 entity in total) |
| Functional Keywords | chchd2, amyloid fibril, protein fibril |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 6 |
| Total formula weight | 68212.49 |
| Authors | Lv, G.,Eliezer, D. (deposition date: 2025-06-04, release date: 2025-07-30, Last modification date: 2025-08-13) |
| Primary citation | Lv, G.,Sayles, N.M.,Huang, Y.,Mancinelli, C.,McAvoy, K.,Shneider, N.A.,Manfredi, G.,Kawamata, H.,Eliezer, D. Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration. Nat Commun, 16:7121-7121, 2025 Cited by PubMed Abstract: Mitochondrial proteins CHCHD10 and CHCHD2 are mutated in rare cases of heritable FTD, ALS and PD and aggregate in tissues affected by these diseases. Here, we show that both proteins form amyloid fibrils and report cryo-EM structures of fibrils formed from their disordered N-terminal domains. The ordered cores of these fibrils are comprised of a region highly conserved between the two proteins, and a subset of the CHCHD10 and CHCHD2 fibril structures share structural similarities and appear compatible with sequence variations in this region. In contrast, disease-associated mutations p.S59L in CHCHD10 and p.T61I in CHCHD2, situated within the ordered cores of these fibrils, cannot be accommodated by the wildtype structures and promote different protofilament folds and fibril structures. These results link CHCHD10 and CHCHD2 amyloid fibrils to neurodegeneration and further suggest that fibril formation by the WT proteins could also be involved in disease etiology. PubMed: 40753073DOI: 10.1038/s41467-025-62149-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.03 Å) |
Structure validation
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