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TitleATTRv-V30M amyloid fibrils from heart and nerves exhibit structural homogeneity.
Journal, issue, pagesStructure, Vol. 32, Issue 12, Page 2244-22250.e3, Year 2024
Publish dateDec 5, 2024
AuthorsBinh An Nguyen / Shumaila Afrin / Anna Yakubovska / Virender Singh / Rose Pedretti / Parker Bassett / Maja Pekala / Jaime Vaquer Alicea / Peter Kunach / Lanie Wang / Andrew Lemoff / Barbara Kluve-Beckerman / Lorena Saelices /
PubMed AbstractAmyloidogenic transthyretin (ATTR) amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made of transthyretin. Transthyretin is primarily produced in tetrameric form ...Amyloidogenic transthyretin (ATTR) amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made of transthyretin. Transthyretin is primarily produced in tetrameric form by the liver, but also by retinal epithelium and choroid plexus. The deposition of these fibrils in the myocardium and peripheral nerves causes cardiomyopathies and neuropathies, respectively. Using cryoelectron microscopy (cryo-EM), we investigated fibrils extracted from cardiac and nerve tissues of an ATTRv-V30M patient. We found consistent fibril structures from both tissues, similar to cardiac fibrils previously described, but different from vitreous humor fibrils of the same genotype. Our findings, along with previous ATTR fibrils structural studies, suggest a uniform fibrillar architecture across different tissues when transthyretin originates from the liver. This study advances our understanding of how deposition and production sites influence fibril structure in ATTRv-V30M amyloidosis.
External linksStructure / PubMed:39423808 / PubMed Central
MethodsEM (helical sym.)
Resolution3.14 - 3.36 Å
Structure data

45039

9byn

EMDB-45039, PDB-9byn:
Cryo-EM structure of amyloid fibril extracted from nerve of a variant ATTR V30M amyloidosis patient
Method: EM (helical sym.) / Resolution: 3.36 Å

45074

9bzs

EMDB-45074, PDB-9bzs:
Cryo-EM structure of cardiac amyloid fibril from a variant ATTR V30M amyloidosis patient
Method: EM (helical sym.) / Resolution: 3.14 Å

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / Amyloidosis / Systemic amyloidosis / ATTR / nerve / cardiac

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