Structural mapping of an aggregation nucleation site in a molten globule intermediate

被引:52
作者
Hammarström, P
Persson, M
Freskgård, PO
Mårtensson, LG
Andersson, D
Jonsson, BH
Carlsson, U [1 ]
机构
[1] Linkoping Univ, Dept Phys Measurement Technol, SE-58183 Linkoping, Sweden
[2] Linkoping Univ, Dept Chem, SE-58183 Linkoping, Sweden
[3] Umea Univ, Dept Biochem, SE-90187 Umea, Sweden
[4] Novo Nordisk AS, Tissue Factor Factor VII Res, DK-2760 Malov, Denmark
关键词
D O I
10.1074/jbc.274.46.32897
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein aggregation plays an important role in biotechnology and also causes numerous diseases. Human carbonic anhydrase II is a suitable model protein for studying the mechanism of aggregation. We found that a molten globule state of the enzyme formed aggregates. The intermolecular interactions involved in aggregate formation were localized in a direct way by measuring excimer formation between each of 20 site-specific pyrene-labeled cysteine mutants. The contact area of the aggregated protein was very specific, and all sites included in the intermolecular interactions were located in the large beta-sheet of the protein, within a limited region between the central beta-strands 4 and 7. This substructure is very hydrophobic, which underlines the importance of hydrophobic interactions between specific beta-sheet containing regions in aggregate formation.
引用
收藏
页码:32897 / 32903
页数:7
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