Orb2 shares common features with the pathological amyloidogenic pathway.

<p><b>(A)</b> Δ<i>L</i><sub><i>c</i></sub> and <i>F</i> SMFS histograms of pFS-2 polyproteins carrying the Q/N-rich PLD of Orb2A show a broad mechanical polymorphism in terms of the increased contour length (Δ<i>L</i><sub><i>c</i></sub>, top) and mechanical stability (bottom), ranging from NM conformers (orange bars) to different M conformers (red bars, <i>n</i> = 106), similar to that found in pathological amyloids [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002361#pbio.1002361.ref041" target="_blank">41</a>]. In line with its reduced ability to form amyloids (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002361#pbio.1002361.g003" target="_blank">Fig 3</a> and <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002361#pbio.1002361.s005" target="_blank">S4 Fig</a>), the mechanical conformational polymorphism of the F5Y mutant is diminished, increasing the proportion of NM conformers (<i>n</i> = 109). <b>(B)</b> Immunodot blot showed that like toxic oligomeric intermediates of other amyloidogenic proteins, both full-length Orb2A, and to a lesser extent Orb2B, as well as their isolated PLDs, are recognized by the A11 antibody [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002361#pbio.1002361.ref045" target="_blank">45</a>]. <b>(C)</b> A representative electron micrograph of aged Orb2A PLD shows the formation oligomers (asterisks) and typical unbranched amyloid fibers (arrows) resembling those of the full-length Orb2A (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002361#pbio.1002361.g001" target="_blank">Fig 1G</a>) and pathological amyloids. Scale bar: 0.2 <i>μ</i>m. Like pathological amyloids, those species are recognized by the fiber-specific OC monoclonal antibody [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002361#pbio.1002361.ref046" target="_blank">46</a>]. For panels B and C, A<i>β</i>42 oligomers and fibers were used as positive controls for the A11 and OC antibodies, respectively, while ubiquitin was used as a negative control. The underlying data for panels in this figure can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002361#pbio.1002361.s001" target="_blank">S1 Data</a>.</p>