Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis

被引：973

作者：

Booth, DR

Sunde, M

Bellotti, V

Robinson, CV

Hutchinson, WL

Fraser, PE

Hawkins, PN

Dobson, CM

Radford, SE

Blake, CCF

Pepys, MB

机构：

[1] HAMMERSMITH HOSP, ROYAL POSTGRAD MED SCH, IMMUNOL MED UNIT, LONDON W12 0NN, ENGLAND

[2] UNIV OXFORD, LAB MOL BIOPHYS, OXFORD OX1 3QT, ENGLAND

[3] UNIV OXFORD, OXFORD CTR MOL SCI, NEW CHEM LAB, OXFORD OX1 3QT, ENGLAND

[4] UNIV TORONTO, CTR RES NEURODEGENERAT DIS, TORONTO, ON M5S 3H2, CANADA

来源：

NATURE | 1997年 / 385卷 / 6619期

关键词：

D O I：

10.1038/385787a0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Tissue deposition of soluble proteins as amyloid fibrils underlies a range of fatal diseases. The two naturally occurring human lysozyme variants are both amyloidogenic, and are shown here to be unstable. They aggregate to form amyloid fibrils with transformation of the mainly helical native fold, observed in crystal structures, to the amyloid fibril cross-beta fold. Biophysical studies suggest that partly folded intermediates are involved in fibrillogenesis, and this may be relevant to amyloidosis generally.

引用

页码：787 / 793

页数：7

共 48 条

[1] INCREASED BODY-TEMPERATURE ACCELERATES AGGREGATION OF THE LEU-68 -] GLN MUTANT CYSTATIN-C, THE AMYLOID-FORMING PROTEIN IN HEREDITARY CYSTATIN-C AMYLOID ANGIOPATHY [J].