• Open Access

Site-Specific Identification of an Aβ Fibril–Heparin Interaction Site by Using Solid-State NMR Spectroscopy

Authors


  • The work was funded by the Wellcome Trust (grant number 088563/B/09/Z). The UK 850 MHz solid-state NMR Facility was funded by EPSRC, BBSRC, and the University of Warwick, including funding through Birmingham Science City Advanced Materials Projects 1 and 2 supported by Advantage West Midlands and the European Regional Development Fund. We thank James Ault, University of Leeds, for mass spectrometry, Mark Tully, University of Liverpool, for heparinase enzyme, and Dinu Iuga, University of Warwick, for his assistance with the 850 MHz SSNMR. The clone for Aβ was kindly provided by Sara Linse, Lund University, and Dominic Walsh, Harvard Institute of Medicine. Aβ fibril seeds and pdb coordinate files were generously provided by Robert Tycko, NIH, Bethesda (USA).

Abstract

original image

At the surface of Aβ1-40 amyloid fibrils that have a threefold molecular symmetry (green in the left picture) a site of interaction of the glycosaminoglycan analogue heparin (blue) was identified. The binding site consists of residues at the N terminus and the turn regions defining the apices of the triangular geometry. Heparin has a lower affinity for Aβ1-40 fibrils having twofold molecular symmetry, thus revealing a remarkable morphological selectivity.

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