Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/172183
Title: Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers
Author: Puig Gomà-Camps, Eduard
Tolchard, James
Riera i Escalé, Antoni
Carulla Casanovas, Natàlia
Keywords: Malaltia d'Alzheimer
Oligòmers
Alzheimer's disease
Oligomers
Issue Date: 11-Sep-2020
Publisher: American Chemical Society
Abstract: Somatostatin (SST14) is strongly related to Alzheimer's disease (AD), as its levels decline during aging, it regulates the proteolytic degradation of the amyloid beta peptide (Aβ), and it binds to Aβ oligomers in vivo. Recently, the 3D structure of a membrane-associated β-sheet pore-forming tetramer (βPFOAβ(1−42) tetramer) has been reported. Here, we show that SST14 binds selectively to the βPFOAβ(1−42) tetramer with a KD value of ∼40 μM without binding to monomeric Aβ(1−42). Specific NMR chemical shift perturbations, observed during titration of SST14, define a binding site in the βPFOAβ(1−42) tetramer and are in agreement with a 2:1 stoichiometry determined by both native mass spectroscopy and isothermal titration calorimetry. These results enabled us to perform driven docking and model the binding mode for the interaction. The present study provides additional evidence on the relation between SST14 and the amyloid cascade and positions the βPFOAβ(1−42) tetramer as a relevant aggregation form of Aβ and as a potential target for AD.
Note: Versió postprint del document publicat a: https://doi.org/10.1021/acschemneuro.0c00470
It is part of: Acs Chemical Neuroscience, 2020, vol. 11, num. 20, p. 3358-3365
URI: http://hdl.handle.net/2445/172183
Related resource: https://doi.org/10.1021/acschemneuro.0c00470
ISSN: 1948-7193
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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