2D IR provides evidence for mobile water molecules in β-amyloid fibrils
Autor: | Robin M. Hochstrasser, Paul H. Axelsen, Liu Liu, Yung Sam Kim |
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Rok vydání: | 2009 |
Předmět: |
Models
Molecular Amyloid beta-Peptides Binding Sites Multidisciplinary Spectrophotometry Infrared Chemistry Kinetics Water Infrared spectroscopy Biological Sciences In Vitro Techniques Fibril Biophysical Phenomena Peptide Fragments Crystallography Residue (chemistry) chemistry.chemical_compound β amyloid Amide Spectroscopy Fourier Transform Infrared Thermodynamics Molecule Binding site Protein Structure Quaternary |
Zdroj: | Proceedings of the National Academy of Sciences. 106:17751-17756 |
ISSN: | 1091-6490 0027-8424 |
Popis: | The motion of water molecules close to amide groups causes their vibrational frequencies to vary rapidly in time. These variations are uniquely sensed by 2-dimensional infrared spectroscopy (2D IR). Here, it is proposed from 2-dimensional experiments on fibrils of amyloid β (Aβ)40 that there are water molecules in the fibrils. The spatial locations of the water (D 2 O) were inferred from the responses of 18 amide modes of Aβ40 labeled with 13 C = 18 O. Fast frequency variations were found for residues L17 and V18 and for the apposed residues L34 and V36, suggesting cavities or channels containing mobile water molecules can form between the 2 sheets. Spectroscopic analysis showed that there are 1.2 water molecules per strand in the fibrils. The 13 C = 18 O substitution of 1 residue per strand creates a linear array of isotopologs along the fibril axis that manifests clearly identifiable vibrational transitions. Here, it is shown from the distributions of amide-I′ vibrational frequencies that the regularity of these chains is strongly residue dependent and in most cases the distorted regions are also those associated with the putative mobile water molecules. It is proposed that Aβ40 fibrils contain structurally significant mobile water molecules within the intersheet region. |
Databáze: | OpenAIRE |
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