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Amyloid Fibers are Water-Filled Nanotubes

Proceedings of the National Academy of Sciences - PNAS, 2002-04, Vol.99 (8), p.5591-5595 [Peer Reviewed Journal]

Copyright 1993-2002 National Academy of Sciences of the United States of America ;Copyright National Academy of Sciences Apr 16, 2002 ;Copyright © 2002, The National Academy of Sciences 2002 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.042681399 ;PMID: 11960014

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Title:
Amyloid Fibers are Water-Filled Nanotubes
Author: Perutz, M. F. ; Finch, J. T. ; Berriman, J. ; Lesk, A.
Subjects: Alzheimer Disease - metabolism ; Amides ; Amyloid - chemistry ; Amyloids ; Asparagine - chemistry ; Average linear density ; Biological Sciences ; Crystallography, X-Ray ; Cylinders ; Electron micrographs ; Exons ; Fourier Analysis ; Fourier transformations ; Fungal Proteins - metabolism ; Glutamine - chemistry ; Humans ; Huntingtin Protein ; Hydrogen Bonding ; Hydrogen bonds ; Microscopy, Electron ; Nanotubes ; Nerve Tissue Proteins - chemistry ; Neurodegenerative diseases ; Nuclear Proteins - chemistry ; Peptide Termination Factors ; Peptides ; Peptides - chemistry ; Prions - chemistry ; Protein Structure, Secondary ; Saccharomyces cerevisiae Proteins ; X ray diffraction ; X-rays
Is Part Of: Proceedings of the National Academy of Sciences - PNAS, 2002-04, Vol.99 (8), p.5591-5595
Description: A study of papers on amyloid fibers suggested to us that cylindrical β-sheets are the only structures consistent with some of the x-ray and electron microscope data. We then found that our own 7-year-old and hitherto enigmatic x-ray diagram of poly-L-glutamine fits a cylindrical sheet of 31 Å diameter made of β-strands with 20 residues per helical turn. Successive turns are linked by hydrogen bonds between both the main chain and side chain amides, and side chains point alternately into and out of the cylinder. Fibers of the exon-1 peptide of huntingtin and of the glutamine- and asparagine-rich region of the yeast prion Sup35 give the same underlying x-ray diagrams, which show that they have the same structure. Electron micrographs show that the 100-Å-thick fibers of the Sup35 peptide are ropes made of three protofibrils a little over 30 Å thick. They have a measured mass of 1,450 Da/Å, compared with 1,426 Da/Å for a calculated mass of three protofibrils each with 20 residues per helical turn wound around each other with a helical pitch of 510 Å. Published x-ray diagrams and electron micrographs show that fibers of synuclein, the protein that forms the aggregates of Parkinson disease, consist of single cylindrical β-sheets. Fibers of Alzheimer Aβ fragments and variants are probably made of either two or three concentric cylindrical β-sheets. Our structure of poly-L-glutamine fibers may explain why, in all but one of the neurodegenerative diseases resulting from extension of glutamine repeats, disease occurs when the number of repeats exceeds 37-40. A single helical turn with 20 residues would be unstable, because there is nothing to hold it in place, but two turns with 40 residues are stabilized by the hydrogen bonds between their amides and can act as nuclei for further helical growth. The Aβ peptide of Alzheimer's disease contains 42 residues, the best number for nucleating further growth. All these structures are very stable; the best hope for therapies lies in preventing their growth.
Publisher: United States: National Academy of Sciences
Language: English
Identifier: ISSN: 0027-8424
EISSN: 1091-6490
DOI: 10.1073/pnas.042681399
PMID: 11960014
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central

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Amyloid Fibers are Water-Filled Nanotubes

Copyright 1993-2002 National Academy of Sciences of the United States of America ;Copyright National Academy of Sciences Apr 16, 2002 ;Copyright © 2002, The National Academy of Sciences 2002 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.042681399 ;PMID: 11960014

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