The Prion Protein N1 and N2 Cleavage Fragments Bind to Phosphatidylserine and Phosphatidic Acid; Relevance to Stress-Protection Responses

PLoS One

Steven J. Collins¹  Cathryn L. Haigh¹  Simon C. Drew²  Carolin Tumpach² 

[1] Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Melbourne Brain Centre, Melbourne, VIC, AUS, 3010;The Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne Brain Centre, Melbourne, VIC, AUS, 3010

关键词: Lipids;    Cell membranes;    Lipid signaling;    Signal peptides;    Cell binding;    Reactive oxygen species;    Lipid mediators;    Proline;   

DOI  :  10.1371/journal.pone.0134680

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Internal cleavage of the cellular prion protein generates two well characterised N-terminal fragments, N1 and N2. These fragments have been shown to bind to anionic phospholipids at low pH. We sought to investigate binding with other lipid moieties and queried how such interactions could be relevant to the cellular functions of these fragments. Both N1 and N2 bound phosphatidylserine (PS), as previously reported, and a further interaction with phosphatidic acid (PA) was also identified. The specificity of this interaction required the N-terminus, especially the proline motif within the basic amino acids at the N-terminus, together with the copper-binding region (unrelated to copper saturation). Previously, the fragments have been shown to be protective against cellular stresses. In the current study, serum deprivation was used to induce changes in the cellular lipid environment, including externalisation of plasma membrane PS and increased cellular levels of PA. When copper-saturated, N2 could reverse these changes, but N1 could not, suggesting that direct binding of N2 to cellular lipids may be part of the mechanism by which this peptide signals its protective response.

【 授权许可】

CC BY