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The lifetime of a 11 complex of httex1 with profilin, determined using a shorter huntingtin variant containing only a single polyproline tract, is shown to be on the submillisecond timescale (τ ex ∼ 600 μs and K diss ∼ 50 μM). Finally, we demonstrate that, in stable profilin-httex1 complexes, the productive oligomerization pathway, leading to the formation of helical coiled-coil httex1 tetramers, is completely abolished, and only the pathway resulting in "nonproductive" dimers remains active, thereby providing a mechanistic basis for ho
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