Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Nature Publishing Group full text link Nature Publishing Group Free PMC article
Full text links

Actions

Share

.2005 Jun 9;435(7043):773-8.
doi: 10.1038/nature03680.

Structure of the cross-beta spine of amyloid-like fibrils

Affiliations

Structure of the cross-beta spine of amyloid-like fibrils

Rebecca Nelson et al. Nature..

Abstract

Numerous soluble proteins convert to insoluble amyloid-like fibrils that have common properties. Amyloid fibrils are associated with fatal diseases such as Alzheimer's, and amyloid-like fibrils can be formed in vitro. For the yeast protein Sup35, conversion to amyloid-like fibrils is associated with a transmissible infection akin to that caused by mammalian prions. A seven-residue peptide segment from Sup35 forms amyloid-like fibrils and closely related microcrystals, from which we have determined the atomic structure of the cross-beta spine. It is a double beta-sheet, with each sheet formed from parallel segments stacked in register. Side chains protruding from the two sheets form a dry, tightly self-complementing steric zipper, bonding the sheets. Within each sheet, every segment is bound to its two neighbouring segments through stacks of both backbone and side-chain hydrogen bonds. The structure illuminates the stability of amyloid fibrils, their self-seeding characteristic and their tendency to form polymorphic structures.

PubMed Disclaimer

Conflict of interest statement

Competing Interests Statement The authors declare that they have no competing financial interests.

Figures

Figure 1
Figure 1
The NNQQNY microcrystal used for X-ray diffraction data collection, held to the tip of a glass capillary by cryoprotectant (50% ethylene glycol/water); scale bar shows 10 μm. X-rays were focused on the encircled areas. Separate data sets were collected for each and were merged to provide the final data set. The inset shows an SEM photograph of NNQQNY crystals, suggesting that the ‘large’ microcrystals used for data collection are composed of several aligned, nanometer-sized blocks; scale bar shows 1 μm.
Figure 2
Figure 2
Structure of GNNQQNY. Unless otherwise noted, carbon atoms are coloured in purple or grey/white, oxygen in red, and nitrogen in blue. a, The pair-of-sheets structure of the fibril-forming peptide GNNQQNY, showing the backbone of each β-strand as an arrow, with ball and stick sidechains protruding. The dry interface is between the two sheets, with the wet interfaces on the outside surfaces. Sidechains Asn2, Gln4 and Asn6 point inwards, forming the dry interface. The 21 screw axis of the crystal is shown as the vertical line. It rotates one of the strands of the near sheet 180° about the axis and moves it up 4.87 Å/2 so that it is superimposed on one of the strands of the far sheet. b, The steric zipper viewed edge on (down thea axis). Notice the vertical shift of one sheet relative to the other, allowing interdigitation of the sidechains emanating from each sheet. The amide stacks of the dry interface are shaded in grey at the center, and those of the wet interface are shaded in pale red on either side. c, The GNNQQNY crystal viewed down the sheets (i.e. from the top of panel a, along theb axis). Six rows of β-sheets run horizontally. Peptide molecules are shown in black and water molecules are represented by red +. Notice that the sheets are in pairs, with a closely spaced pair (8.5 Å) alternating with a wider spaced (15 Å) pair. The wide spaces between sheets (wet interfaces) are filled with water molecules, whereas the closely spaced interfaces (dry interfaces) lack waters, other than those hydrating the caroboxylate ions at the C-termini of peptides. The atoms in the lower left unit cell are shown as spheres representing van der Waals radii. d, The steric zipper. This is a close-up view of a pair of GNNQQNY molecules from the same view as panel c, showing the remarkable shape complementarity of the Asn and Gln sidechains protruding into the dry interface. 2Fo-Fc electron density is shown, and the position of the central screw axis is indicated. e, Views of the β-sheets from the side (down thec axis), showing 3 β-strands with the inter-strand hydrogen bonds. Sidechain carbon atoms are highlighted in yellow. Backbone hydrogen bonds are shown by purple or black dots and sidechain hydrogen bonds by yellow dots. The length of each hydrogen bond is noted in Å units. The views of the interfaces are close to the views of panel a, where purple or grey/white backbone carbons correspond between equivalent sheets. The left hand set of three strands is viewed from the centre of the dry interface; the right hand set of three strands is viewed from the wet interface. Notice the amide stacks in both interfaces and the tyrosine stack in the wet interface. Also, notice that the wet interface is offset along the vertical axis by one half of the interstrand separation of 4.87 Å
Figure 3
Figure 3
A conjectural plot of the free energy, G, for conversion of monomeric GNNQQNY, M, to the aggregated state, Mn. The standard free energy change ΔG0 for the conversion is small, so that the change in ΔG is controlled mainly by the concentration of monomer. At low concentrations, the monomeric state is favoured over the aggregated state, and the aggregated state is favoured at high concentrations. There is a significant kinetic barrier to formation of the aggregated state, ΔG‡ formation. At high concentrations of protein, the barrier to redissolve fibers, ΔG‡ dissolution, is very large.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Sipe JD, Cohen AS. Review: history of the amyloid fibril. J Struct Biol. 2000;130:88–98. - PubMed
    1. Cohen AS, Calkins E. Electron microscopic observations on a fibrous component in amyloid of diverse origins. Nature. 1959;183:1202–3. - PubMed
    1. Eanes ED, Glenner GG. X-ray diffraction studies on amyloid filaments. J Histochem Cytochem. 1968;16:673–7. - PubMed
    1. Geddes AJ, Parker KD, Atkins ED, Beighton E. “Cross-beta” conformation in proteins. J Mol Biol. 1968;32:343–58. - PubMed
    1. Sunde M, et al. Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J Mol Biol. 1997;273:729–39. - PubMed

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full text links
Nature Publishing Group full text link Nature Publishing Group Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp