Movie
Controller
Structure viewers
About Yorodumi Papers
+Search query
-Structure paper
| Title | Structural dependence of HET-s amyloid fibril infectivity assessed by cryoelectron microscopy. |
|---|---|
| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 108, Issue 8, Page 3252-3257, Year 2011 |
| Publish date | Feb 22, 2011 |
 Authors | Naoko Mizuno / Ulrich Baxa / Alasdair C Steven /  |
| PubMed Abstract | HET-s is a prion protein of the fungus Podospora anserina which, in the prion state, is active in a self/nonself recognition process called heterokaryon incompatibility. Its prionogenic properties ...HET-s is a prion protein of the fungus Podospora anserina which, in the prion state, is active in a self/nonself recognition process called heterokaryon incompatibility. Its prionogenic properties reside in the C-terminal "prion domain." The HET-s prion domain polymerizes in vitro into amyloid fibrils whose properties depend on the pH of assembly; above pH 3, infectious singlet fibrils are produced, and below pH 3, noninfectious triplet fibrils. To investigate the correlation between structure and infectivity, we performed cryo-EM analyses. Singlet fibrils have a helical pitch of approximately 410 Å and a left-handed twist. Triplet fibrils have three protofibrils whose lateral dimensions (36 × 25 Å) and axial packing (one subunit per 9.4 Å) match those of singlets but differ in their supercoiling. At 8.5-Å resolution, the cross-section of the singlet fibril reconstruction is largely consistent with that of a β-solenoid model previously determined by solid-state NMR. Reconstructions of the triplet fibrils show three protofibrils coiling around a common axis and packed less tightly at pH 3 than at pH 2, eventually peeling off. Taken together with the earlier observation that fragmentation of triplet fibrils by sonication does not increase infectivity, these observations suggest a novel mechanism for self-propagation, whereby daughter fibrils nucleate on the lateral surface of singlet fibrils. In triplets, this surface is occluded, blocking nucleation and thereby explaining their lack of infectivity. |
 External links | Proc Natl Acad Sci U S A / PubMed:21300906 / PubMed Central |
| Methods | EM (helical sym.) |
| Resolution | 8.5 Å |
| Structure data |  EMDB-2946: |
| Source |
|
Podospora anserina (fungus)