title: Heparin acts as a structural component of β-endorphin amyloid fibrils rather than a simple aggregation promoter.
abstract: The aggregation promoter heparin is commonly used to study the aggregation kinetics and biophysical properties of protein amyloids. However, the underlying mechanism for amyloid promotion by heparin remains poorly understood. In the case of the neuropeptide β-endorphin that can reversibly adopt a functional amyloid form in nature, aggregation in the presence of heparin leads to a loss of function. Applying correlative optical super-resolution microscopy methods, we show that heparin incorporates into emerging β-endorphin fibrils forming an integral component and is essential for amyloid templating. This will have direct implications on β-endorphin's normal physiological function and raises concerns on the biological relevance of heparin-promoted amyloid models.
authors.affiliation: Laser Analytics Group, Department of Chemical Engineering and Biotechnology, Cambridge University, Pembroke Street, Cambridge, CB2 3RA, UK. cfk23@cam.ac.uk.
authors.forename: N
authors.initials: N
authors.lastname: Nespovitaya
authors.affiliation: Laser Analytics Group, Department of Chemical Engineering and Biotechnology, Cambridge University, Pembroke Street, Cambridge, CB2 3RA, UK. cfk23@cam.ac.uk.
authors.forename: P
authors.initials: P
authors.lastname: Mahou
authors.affiliation: Laser Analytics Group, Department of Chemical Engineering and Biotechnology, Cambridge University, Pembroke Street, Cambridge, CB2 3RA, UK. cfk23@cam.ac.uk.
authors.forename: R F
authors.initials: RF
authors.lastname: Laine
authors.affiliation: Laser Analytics Group, Department of Chemical Engineering and Biotechnology, Cambridge University, Pembroke Street, Cambridge, CB2 3RA, UK. cfk23@cam.ac.uk.
authors.forename: G S Kaminski
authors.initials: GSK
authors.lastname: Schierle
authors.affiliation: Laser Analytics Group, Department of Chemical Engineering and Biotechnology, Cambridge University, Pembroke Street, Cambridge, CB2 3RA, UK. cfk23@cam.ac.uk.
authors.forename: C F
authors.initials: CF
authors.lastname: Kaminski
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D008853:Microscopy; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D001615:beta-Endorphin / Q000737:chemistry*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D066329:Protein Aggregates; D001615:beta-Endorphin; D006493:Heparin