Journal
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
Volume 23, Issue 2, Pages 67-75Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/13506129.2016.1168292
Keywords
AA amyloidosis; amyloid fibril; glycosaminoglycan; serum amyloid A; sulfate group
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Funding
- Strategic Research Foundation Grant-aided Project for Private Universities from the Ministry of Education, Culture, Sports, Science, and Technology, Japan [S1201040]
- JSPS KAKENHI [15K08436]
- KEIRIN RACE
- Grants-in-Aid for Scientific Research [15J12051, 15K08436, 25460080, 16H05088, 25293014] Funding Source: KAKEN
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Serum amyloid A (SAA) is a precursor protein of amyloid fibrils. Given that heparan sulfate (HS), a glycosaminoglycan (GAG), is detected in amyloid deposits, it has been suggested that GAG is a key component of amyloid fibril formation. We previously reported that heparin (an analog of HS) facilitates the fibril formation of SAA, but the structural requirements remain unknown. In the present study, we investigated the structural requirements of GAGs for facilitating the amyloid fibril formation of SAA. Spectroscopic analyses using structurally diverse GAG analogs suggested that the fibril formation of SAA was facilitated irrespective of the backbone structure of GAGs; however, the facilitating effect was strongly correlated with the degree of sulfation. Microscopic analyses revealed that the morphologies of SAA aggregates were modulated by the GAGs. The HS molecule, which is less sulfated than heparin but contains highly sulfated domains, exhibited a relatively high potential to facilitate fibril formation compared to other GAGs. The length dependence of fragmented heparins on the facilitating effect suggested that a high density of sulfate groups is also required. These results indicate that not only the degree of sulfation but also the lengths of sulfated domains in GAG play important roles in fibril formation of SAA.
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