Amyloid fibril formation by pulmonary surfactant protein C

FEBS Letters

Johansson, Jan²  Eliasson, Erik⁴  Gustafsson, Magnus²  Thyberg, Johan¹  Näslund, Jan³ 

[1] Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, S-171 77 Stockholm, Sweden;Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden;Department of Clinical Neuroscience, Karolinska Institutet, S-141 86 Huddinge, Sweden;Department of Environmental Medicine, Karolinska Institutet, S-171 77 Stockholm, Sweden

关键词: Amyloid fibril;    Lipid-associated peptide;    Protein palmitoylation;    Pulmonary surfactant;    Surfactant protein C;    BAL;    bronchoalveolar lavage;    GM-CSF;    granulocyte macrophage colony-stimulating factor;    PAP;    pulmonary alveolar proteinosis;    SP;    surfactant protein;   

DOI  :  10.1016/S0014-5793(99)01692-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Lung surfactant protein C (SP-C) is a lipopeptide that contains two fatty acyl (palmitoyl) chains bound via intrinsically labile thioester bonds. SP-C can transform from a monomeric α-helix into β-sheet aggregates, reminiscent of structural changes that are supposed to occur in amyloid fibril formation. SP-C is here shown to form amyloid upon incubation in solution. Furthermore, one patient with pulmonary alveolar proteinosis (PAP, a rare disease where lung surfactant proteins and lipids accumulate in the airspaces) and six healthy controls have been studied regarding presence and composition of amyloid fibrils in the cell-free fraction of bronchoalveolar lavage (BAL) fluid. Abundant amyloid fibrils were found in BAL fluid from the patient with PAP and, in low amounts, in three of the six healthy controls. SDS-insoluble fibrillar material associated with PAP mainly consists of SP-C, in contrast to the fibrils found in controls. Fibrillated SP-C has to a significant extent lost the palmitoyl groups, and removal of the palmitoyl groups in vitro increases the rate of fibril formation.

【 授权许可】

Unknown