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Structural basis fo...
Structural basis for transthyretin amyloid formation in vitreous body of the eye
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- Iakovleva, Irina (author)
- Umeå universitet,Kemiska institutionen
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- Hall, Michael, 1980- (author)
- Umeå universitet,Kemiska institutionen
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- Oelker, Melanie (author)
- Umeå universitet,Kemiska institutionen
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- Sandblad, Linda (author)
- Umeå universitet,Kemiska institutionen
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- Anan, Intissar (author)
- Umeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Avdelningen för medicin
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- Sauer-Eriksson, A. Elisabeth (author)
- Umeå universitet,Kemiska institutionen
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(creator_code:org_t)
- 2021-12-08
- 2021
- English.
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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https://umu.diva-por... (primary) (Raw object)
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Abstract
Subject headings
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- Amyloid transthyretin (ATTR) amyloidosis is characterized by the abnormal accumulation of ATTR fibrils in multiple organs. However, the structure of ATTR fibrils from the eye is poorly understood. Here, we used cryo-EM to structurally characterize vitreous body ATTR fibrils. These structures were distinct from previously characterized heart fibrils, even though both have the same mutation and type A pathology. Differences were observed at several structural levels: in both the number and arrangement of protofilaments, and the conformation of the protein fibril in each layer of protofilaments. Thus, our results show that ATTR protein structure and its assembly into protofilaments in the type A fibrils can vary between patients carrying the same mutation. By analyzing and matching the interfaces between the amino acids in the ATTR fibril with those in the natively folded TTR, we are able to propose a mechanism for the structural conversion of TTR into a fibrillar form.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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