9ZLD
Cryo-EM structure of hepatic amyloid fibril from a variant ATTRV122delta, single filament morphology
Summary for 9ZLD
| Entry DOI | 10.2210/pdb9zld/pdb |
| Related | 9BDM 9BDR |
| EMDB information | 44462 44466 44467 74399 |
| Descriptor | Transthyretin (1 entity in total) |
| Functional Keywords | attr, systemic amyloidosis, v122delta, amyloid, protein fibril |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 5 |
| Total formula weight | 68391.14 |
| Authors | |
| Primary citation | Ahmed, Y.,Nguyen, B.A.,Kelly, C.,Afrin, S.,Singh, V.,Evers, B.M.,Shelton, J.M.,Lopez Escobar, C.,Singh, P.,Pedretti, R.,Wang, L.,Bassett, P.,Fernandez-Ramirez, M.D.C.,Pekala, M.,Lemoff, A.,Kluve-Beckerman, B.,Saelices, L. Amyloid fibril polymorphism in the heart and liver of a patient with polyneuropathic ATTRv-V122 Delta amyloidosis. Commun Biol, 2026 Cited by PubMed Abstract: ATTR amyloidosis is a phenotypically heterogeneous disease characterized by the pathological deposition of transthyretin in the form of amyloid fibrils into various organs. ATTR amyloidosis may result from mutations in variant (ATTRv) amyloidosis, or aging in wild-type (ATTRwt) amyloidosis. ATTRwt generally manifests as cardiomyopathy, whereas ATTRv may present as polyneuropathy, cardiomyopathy, or mixed, in combination with many other symptoms deriving from multisystem organ involvement. Over 220 different mutational variants of transthyretin have been identified, many of them being linked to specific disease symptoms. Yet, the role of these mutations in explaining differential disease manifestations remains unclear. Using cryo-electron microscopy, here we structurally characterized fibrils from the heart and the liver of an ATTRv patient carrying the V122∆ mutation, which is predominantly associated with polyneuropathy. Our results show that these fibrils are polymorphic, presenting as both single and double filaments. Our study alludes to a structural connection contributing to phenotypic variation in ATTR amyloidosis, as polymorphism in ATTR fibrils may manifest in patients with predominantly polyneuropathic phenotypes. PubMed: 41917523DOI: 10.1038/s42003-026-09919-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
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