Movie
Controller
Structure viewers
About Yorodumi Papers
+Search query
-Structure paper
| Title | Interprotofilament interactions between Alzheimer's Abeta1-42 peptides in amyloid fibrils revealed by cryoEM. |
|---|---|
| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 106, Issue 12, Page 4653-4658, Year 2009 |
| Publish date | Mar 24, 2009 |
 Authors | Rui Zhang / Xiaoyan Hu / Htet Khant / Steven J Ludtke / Wah Chiu / Michael F Schmid / Carl Frieden / Jin-Moo Lee /  |
| PubMed Abstract | 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 ...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. |
 External links | Proc Natl Acad Sci U S A / PubMed:19264960 / PubMed Central |
| Methods | EM (helical sym.) |
| Resolution | 10.0 Å |
| Structure data |  EMDB-5052: |
