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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2009-3-25
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pubmed:abstractText |
Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of amyloid plaques in the brain. This amyloid primarily contains amyloid-beta (Abeta), a 39- to 43-aa peptide derived from the proteolytic cleavage of the endogenous amyloid precursor protein. The 42-residue-length Abeta peptide (Abeta(1-42)), the most abundant Abeta peptide found in plaques, has a much greater propensity to self-aggregate into fibrils than the other peptides and is believed to be more pathogenic. Synthetic human Abeta(1-42) peptides self-aggregate into stable but poorly-ordered helical filaments. We determined their structure to approximately 10-A resolution by using cryoEM and the iterative real-space reconstruction method. This structure reveals 2 protofilaments winding around a hollow core. Previous hairpin-like NMR models for Abeta(17-42) fit well in the cryoEM density map and reveal that the juxtaposed protofilaments are joined via the N terminus of the peptide from 1 protofilament connecting to the loop region of the peptide in the opposite protofilament. This model of mature Abeta(1-42) fibrils is markedly different from previous cryoEM models of Abeta(1-40) fibrils. In our model, the C terminus of Abeta forms the inside wall of the hollow core, which is supported by partial proteolysis analysis.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-10022824,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-10097098,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-10600563,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-10860734,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-10903851,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-10940227,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-11125866,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-12072564,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-12093917,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-12124300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-12425301,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-12481027,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-12484785,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-12801659,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-15766273,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-15919759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-16039562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-16095615,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-16182533,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-16215229,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-16293696,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-16401079,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-16634632,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-16920151,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-17280549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-1730616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-18483195,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-5723775,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-7490736,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-8490014,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-9268388,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19264960-9356260
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
106
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4653-8
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:19264960-Amino Acid Sequence,
pubmed-meshheading:19264960-Amyloid,
pubmed-meshheading:19264960-Amyloid beta-Peptides,
pubmed-meshheading:19264960-Cryoelectron Microscopy,
pubmed-meshheading:19264960-Humans,
pubmed-meshheading:19264960-Models, Molecular,
pubmed-meshheading:19264960-Molecular Sequence Data,
pubmed-meshheading:19264960-Peptide Fragments,
pubmed-meshheading:19264960-Peptides,
pubmed-meshheading:19264960-Protein Processing, Post-Translational,
pubmed-meshheading:19264960-Static Electricity
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pubmed:year |
2009
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pubmed:articleTitle |
Interprotofilament interactions between Alzheimer's Abeta1-42 peptides in amyloid fibrils revealed by cryoEM.
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pubmed:affiliation |
Graduate Program in Structural and Computational Biology and Molecular Biophysics, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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