Architecture of the Alzheimer’s AβP Ion Channel Pore

Architecture of the Alzheimer’s AβP Ion Channel Pore We have proposed that the cytotoxic action of Alzheimer’s amyloid beta protein might be initiated by the interaction with the neuronal cell membrane, and subsequent formation of toxic ion channels. Consequently, AβP toxicity can be explained on the basis of harmful ion fluxes across AβP channels. The conformation of AβP in membranes is not known. However, several models suggests that a transmembrane annular polymeric structure is responsible for the ion channel properties of the membrane-bound AβP. To identify that portion of the AβP molecule making up the conducting pore we have hypothesized that the region of the AβP sequence in the vicinity of the hypothetical pore might interact with complementary regions in the adjacent AβP subunits. We have further hypothesized that an interaction by a peptide segment would block AβP conductance. To test this hypothesis we synthesized peptides that encompass the histidine dyad (H-H) previously hypothesized to line the pore. We report here that peptides designed to most closely match the proposed pore are, in fact, the most effective at blocking ion currents through the membrane-incorporated AβP channel. As previously shown for Zn2+ blockade, peptide blockade is also asymmetric. The results also provide additional evidence for the asymmetric insertion of the AβP molecules into lipid membranes, and give support to the concept that rings of histidines line the entry to one side of the AβP pore. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Architecture of the Alzheimer’s AβP Ion Channel Pore

Loading next page...
 
/lp/springer_journal/architecture-of-the-alzheimer-s-a-p-ion-channel-pore-uhnkvg36fT
Publisher
Springer-Verlag
Copyright
Copyright © 2004 by Springer-Verlag New York Inc.
Subject
Philosophy
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-003-0638-7
Publisher site
See Article on Publisher Site

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches

$49/month

Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.

$588

$360/year

billed annually
Start Free Trial

14-day Free Trial