Fig. 4: Continuous stepwise slippage of expanded CAG tract.
From: Stick-slip unfolding favors self-association of expanded HTT mRNA
Slipped intermediates of fHTT40 analyzed as in Fig. 1. A Example FEC demonstrating transitions at low force that extend or shorten Lc, before unfolding at 13.2 pN; see Supplementary Figs. 2, 3 for analysis details. Black dashed line: eWLC model for fully folded fHTT40. Blue dashed lines, eWLC fits to structures differing by 2–4 unpaired CAG triplets. Inset: Expansion of low force region. B Distribution of ΔLcMFE for all fHTT mRNAs. Stretch, black; relax; red. C Passive mode fluctuations in ΔLcMFE for fHTT40 at ~6 pN pretension. Black dashed lines show HMM state, red line shows the HMM model. Similar results were obtained when the HMM fit was unconstrained (Supplementary Fig. 9). Hopping rates of 0.9–3 s−1 are comparable to the folding kinetics of a stable 21 bp hairpin33,34. D. Transition density plot from the HMM model in (C). See Supplementary Fig. 10 for data at high force.
