Linker Histone H1 Binds to Disease Associated Amyloid-like Fibrils

• Published in: Journal of molecular biology Vol. 361; no. 3; pp. 493 - 505
• Main Authors: Duce, James A., Smith, David P., Blake, Rachel E., Crouch, Peter J., Li, Qiao-Xin, Masters, Colin L., Trounce, Ian A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 18.08.2006
• Subjects: alpha-Synuclein - chemistry; alpha-Synuclein - metabolism; alpha-Synuclein - ultrastructure; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - ultrastructure; amyloid-like; amyloid-β protein; Animals; Astrocytes - metabolism; Astrocytes - pathology; Brain - metabolism; Brain - pathology; Cells, Cultured; histone H1; Histones - chemistry; Histones - metabolism; Humans; lysozyme; Mice; Mice, Transgenic; Microscopy, Electron, Transmission; Muramidase - chemistry; Muramidase - metabolism; Muramidase - ultrastructure; Neurons - metabolism; Neurons - pathology; Parkinson Disease - metabolism; Parkinson Disease - pathology; Plaque, Amyloid - metabolism; Plaque, Amyloid - ultrastructure; Protein Binding; Recombinant Proteins - chemistry; Surface Plasmon Resonance; α-synuclein; histone H1; AD; lysozyme; EM; PICUP; TOSYL; Aβ; NFTs; PD; SPR; amyloid-β protein; α-synuclein; amyloid-like
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2006.06.038

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most prevalent neurodegenerative diseases of the central nervous system. These two diseases share a common feature in that a normally soluble peptide (amyloid-β) or protein (α-synuclein) aggregates into an ordered fibrillar structure. As well as structural similarities observed between fibrillar aggregates related to these diseases, common pathological processes of increased oxidative injury, excitotoxicity and altered cell cycle are also evident. It was the aim of this study to identify novel interacting proteins to the amyloid-like motif and therefore identify common potential pathways between neurodegenerative diseases that share biophysical properties common to classical amyloid fibrils. Optimal ageing of recombinant proteins to form amyloid-like fibrils was determined by electron microscopy, Congo red birefringement and photo-induced cross-linking. Using pull-down assays the strongest detected interacting protein to the amyloid-like motifs of amyloid-β, α-synuclein and lysozyme was identified as histone H1. The interaction with the amyloid-like motif was confirmed by techniques including surface plasmon resonance and immunohistochemistry. Histone H1 is known to be an integral part of chromatin within the nucleus, with a primary role of binding DNA that enters and exits from the nucleosome, and facilitating the shift in equilibrium of chromatin towards a more condensed form. However, phosphorylated histone H1 is predominantly present in the cytoplasm and as yet the functional significance of this translocation is unknown. This study also found that histone H1 is localised within the cytoplasm of neurons and astrocytes from areas affected by disease as well as amyloid plaques, supporting the hypothesis that histone H1 favoured binding to an ordered fibrillar motif. We conclude that the binding of histone H1 to a general amyloid-like motif indicates that histone H1 may play an important common role in diseases associated with amyloid-like fibrils.