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TitleCommon transthyretin-derived amyloid fibril structures in patients with hereditary ATTR amyloidosis.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 7623, Year 2023
Publish dateNov 22, 2023
AuthorsMaximilian Steinebrei / Julian Baur / Anaviggha Pradhan / Niklas Kupfer / Sebastian Wiese / Ute Hegenbart / Stefan O Schönland / Matthias Schmidt / Marcus Fändrich /
PubMed AbstractSystemic ATTR amyloidosis is an increasingly important protein misfolding disease that is provoked by the formation of amyloid fibrils from transthyretin protein. The pathological and clinical ...Systemic ATTR amyloidosis is an increasingly important protein misfolding disease that is provoked by the formation of amyloid fibrils from transthyretin protein. The pathological and clinical disease manifestations and the number of pathogenic mutational changes in transthyretin are highly diverse, raising the question whether the different mutations may lead to different fibril morphologies. Using cryo-electron microscopy, however, we show here that the fibril structure is remarkably similar in patients that are affected by different mutations. Our data suggest that the circumstances under which these fibrils are formed and deposited inside the body - and not only the fibril morphology - are crucial for defining the phenotypic variability in many patients.
External linksNat Commun / PubMed:37993462 / PubMed Central
MethodsEM (helical sym.)
Resolution2.3673 - 3.39 Å
Structure data

17736

8pke

EMDB-17736, PDB-8pke:
ATTRV20I amyloid fibril from hereditary ATTR amloidosis
Method: EM (helical sym.) / Resolution: 3.39 Å

17737

8pkf

EMDB-17737, PDB-8pkf:
ATTRG47E amyloid fibril from hereditary ATTR amloidosis
Method: EM (helical sym.) / Resolution: 2.3673 Å

17738

8pkg

EMDB-17738, PDB-8pkg:
ATTRV122I amyloid fibril from hereditary ATTR amloidosis
Method: EM (helical sym.) / Resolution: 2.99 Å

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / Transthyretin / ATTR amyloidosis / ATTRV20I / amyloid fibril / misfolding disease / cryo-EM / ATTRG47E / ATTRV122I

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