Hexa-Histidine, a Peptide with Versatile Applications in the Study of Amyloid-β(1-42) Molecular Mechanisms of Action.

Autor: Salazar J; Departamento de Química, Universidad Nacional Autónoma de Nicaragua-León, León 21000, Nicaragua., Samhan-Arias AK; Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), C\Arzobispo Morcillo 4, 28029 Madrid, Spain.; Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), C\Arturo Duperier 4, 28029 Madrid, Spain., Gutierrez-Merino C; Instituto de Biomarcadores de Patologías Moleculares, Universidad de Extremadura, 06006 Badajoz, Spain.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2023 Oct 17; Vol. 28 (20). Date of Electronic Publication: 2023 Oct 17.
DOI: 10.3390/molecules28207138
Abstrakt: Amyloid β (Aβ) oligomers are the most neurotoxic forms of Aβ, and Aβ(1-42) is the prevalent Aβ peptide found in the amyloid plaques of Alzheimer's disease patients. Aβ(25-35) is the shortest peptide that retains the toxicity of Aβ(1-42). Aβ oligomers bind to calmodulin (CaM) and calbindin-D28k with dissociation constants in the nanomolar Aβ(1-42) concentration range. Aβ and histidine-rich proteins have a high affinity for transition metal ions Cu 2+ , Fe 3+ and Zn 2+ . In this work, we show that the fluorescence of Aβ(1-42) HiLyte TM -Fluor555 can be used to monitor hexa-histidine peptide (His 6 ) interaction with Aβ(1-42). The formation of His 6 /Aβ(1-42) complexes is also supported by docking results yielded by the MDockPeP Server. Also, we found that micromolar concentrations of His 6 block the increase in the fluorescence of Aβ(1-42) HiLyte TM -Fluor555 produced by its interaction with the proteins CaM and calbindin-D28k. In addition, we found that the His 6 -tag provides a high-affinity site for the binding of Aβ(1-42) and Aβ(25-35) peptides to the human recombinant cytochrome b 5 reductase, and sensitizes this enzyme to inhibition by these peptides. In conclusion, our results suggest that a His 6 -tag could provide a valuable new tool to experimentally direct the action of neurotoxic Aβ peptides toward selected cellular targets.
Databáze: MEDLINE
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