New structures help the modeling of toxic amyloidbeta ion channels

Trends in Biochemical Sciences
Hyunbum JangRuth Nussinov

Abstract

The mechanism of amyloid toxicity is poorly understood and there are two schools of thought in this hotly debated field: the first favors membrane destabilization by intermediate-to-large amyloid oligomers, with consequent thinning and non-specific ion leakage; the second favors ion-specific permeable channels lined by small amyloid oligomers. Published results currently support both mechanisms. However, the amyloidbeta (Abeta) peptide has recently been shown to form a U-shaped 'beta-strand-turn-beta-strand' structure. This structure and the available physiological data present a challenge for computational biology--to provide candidate models consistent with the experimental data. Modeling based on small Abeta oligomers containing extramembranous N-termini predicts channels with shapes and dimensions consistent with experimentally derived channel structures. These results support the hypothesis that small Abeta oligomers can form ion channels. Molecular dynamics modeling can provide blueprints of 3D structural conformations for many other amyloids whose membrane association is key to their toxicity.

References

Dec 12, 1991·Nature·D J Selkoe
Dec 1, 1994·Biophysical Journal·S R DurellH B Pollard
Nov 23, 1994·Molecular and Cellular Biochemistry·N ArispeE Rojas
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·R EtcheberrigarayD L Alkon
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·N ArispeE Rojas
Feb 27, 1997·Nature·C PetosaR C Liddington
Jun 5, 1998·The Journal of Biological Chemistry·S K RheeR Lal
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M P LambertW L Klein
Aug 14, 1999·Biochimica Et Biophysica Acta·Y SokolovB L Kagan
Feb 19, 2000·Current Opinion in Structural Biology·J C Rochet, P T Lansbury
Mar 22, 2000·Biochemistry·T L BenzingerS C Meredith
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·L C SerpellR A Crowther
Jul 19, 2000·Biochimica Et Biophysica Acta·L C Serpell
Sep 26, 2000·Journal of Neuroscience Research·J I Kourie, A Culverson
Oct 6, 2000·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Y HirakuraB L Kagan
Jun 21, 2001·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Y Hirakura, B L Kagan
Nov 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·H LinR Lal
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·M F PerutzA Lesk
Jul 19, 2002·Nature·Hilal A LashuelPeter T Lansbury
Jul 20, 2002·Peptides·Meng-chin Allison Lin, Bruce L Kagan
Sep 5, 2002·Journal of Neuroscience Research·Marina D KirkitadzeDavid B Teplow
Oct 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·Buyong Ma, Ruth Nussinov
Nov 2, 2002·The EMBO Journal·Marcus Fändrich, Christopher M Dobson
Nov 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Limin WangWilfredo Colon
Jan 30, 2003·The EMBO Journal·Piero Andrea TemussiAnnalisa Pastore
Mar 12, 2004·The Journal of Membrane Biology·N Arispe
Apr 28, 2004·Journal of Molecular Biology·Annalisa ReliniMassimo Stefani
Jun 11, 2004·Biophysical Journal·David L MobleyMarjorie L Longo
Jan 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·O Sumner MakinLouise C Serpell
Jan 11, 2005·Science·Bruce L Kagan
Feb 22, 2005·The Journal of Biological Chemistry·Angelo DemuroCharles G Glabe
Jun 10, 2005·Nature·Rebecca NelsonDavid Eisenberg
Jul 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Arjan QuistRatnesh Lal
Sep 30, 2005·Journal of the American Chemical Society·Sandra Chimon, Yoshitaka Ishii
Nov 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·Thorsten LührsRoland Riek

❮ Previous
Next ❯

Citations

Feb 21, 2014·Molecular Neurobiology·Xiaoguang YangJames C-M Lee
May 7, 2008·The Journal of Physical Chemistry. B·Jie ZhengRuth Nussinov
Feb 4, 2009·Cellular and Molecular Life Sciences : CMLS·R J S VianaC M P Rodrigues
Mar 13, 2009·Journal of the American Chemical Society·Pieter E S SmithAyyalusamy Ramamoorthy
Mar 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hyunbum JangRatnesh Lal
May 25, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nicholas B LastAndrew D Miranker
Mar 2, 2013·Physical Chemistry Chemical Physics : PCCP·Hyunbum JangRuth Nussinov
Mar 16, 2013·Physical Chemistry Chemical Physics : PCCP·Xiang YuJie Zheng
Oct 26, 2011·The Journal of Cell Biology·Angelo DemuroIan Parker
Dec 25, 2015·Journal of the American Chemical Society·Thanh D DoMichael T Bowers
Jan 8, 2013·Archives of Medical Research·David OrmeñoJorge Parodi
Nov 24, 2011·Journal of Molecular Biology·Xiang Yu, Jie Zheng
Oct 26, 2010·Journal of Molecular Biology·Hyunbum JangRuth Nussinov
Nov 13, 2008·Brain Research Bulletin·Ying NiuYandao Gong
Mar 13, 2009·Journal of Cellular and Molecular Medicine·Katherine A PriceCyril C Curtain
Nov 22, 2012·Journal of Cellular Physiology·Ivana SirangeloMaria Luisa Balestrieri
Apr 30, 2013·Glia·Ilaria PradaClaudia Verderio
Jul 14, 2010·Angewandte Chemie·Sara M Butterfield, Hilal A Lashuel
Nov 9, 2011·Proteomics·Laura Di FrancescoM Eugenia Schininà
Apr 6, 2016·Neuroscience and Biobehavioral Reviews·Riqiang YanRobert Vassar
Sep 1, 2012·Biochimica Et Biophysica Acta·Jun ZhaoJie Zheng
Sep 15, 2012·Biochimica Et Biophysica Acta·Chetan PoojariBirgit Strodel
Oct 25, 2008·Journal of Molecular Biology·Junping YuYuri L Lyubchenko
Aug 18, 2010·Biophysical Journal·Karine BerthelotChristophe Cullin
Nov 12, 2013·Biophysical Journal·Kshitij GuptaRobert Blumenthal
Nov 26, 2013·Biophysical Journal·Chetan PoojariBirgit Strodel
Dec 20, 2013·Physical Chemistry Chemical Physics : PCCP·Jun ZhaoJie Zheng

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.