Biology subjects

Drechsler, H.

Publications and source records attributed to Drechsler, H..

3 recordsLinked to original sources

bioRxiv2024

The kinesin Kip2 promotes microtubule growth using a bipartite polymerase module to deliver tubulin to microtubule plus-ends

Kinesin molecular motors are essential for fundamental cellular processes such as chromosome segregation or vesicular transport. To fulfil their function, some kinesins promote microtubule growth, but the molecular mechanism underlying this activity remains unclear. One of the motors with the strongest microtubule growth-promoting activity is Kip2, a kinesin that is required for astral microtubule integrity and spindle positioning in yeast. Here we show that the ability of Kip2 to polymerize microtubules is coupled to binding and transport of free tubulin. We report that the Kip2 N-terminus is required to promote microtubule elongation in vitro and in vivo. Kip2 binds free tubulin through this unstructured, basic domain and delivers it to microtubule plus-ends. In addition to the N-terminus, we find that ATP hydrolysis and motor activity is also required for microtubule polymerisation. Finally, transfer of the Kip2 N-terminus to kinesin-1, a kinesin that lacks polymerase activity, transforms kinesin-1 into a tubulin-transporting microtubule polymerase. We propose that motor-driven tubulin delivery to microtubule plus-ends is an efficient mechanism used by kinesins to promote microtubule polymerization.

cell biology↗

bioRxiv2023

Self-assembly and contraction of micron-scale DNA rings

Contractile rings formed from cytoskeletal filaments mediate the division of cells. The reverse-engineering of synthetic contractile rings could shed light on fundamental physical principles of the ring self-assembly and dynamics independent of the natural protein-based compounds. Here, we engineer DNA nanotubes and crosslink them with a synthetic peptide-functionalized star-PEG construct. The star-PEG construct induces the formation of DNA nanotube bundles composed of several tens of individual DNA nanotubes. Importantly, the DNA nanotube bundles curve into closed micron-scale DNA rings in a high-yield one-pot self-assembly process resulting in several thousand rings per microliter. The crosslinked DNA rings can undergo contraction to less than half of their initial diameter by two distinct mechanisms, triggered by increasing molecular crowding or temperature. DNA-based contractile rings expand the toolbox of DNA nanotechnology and could be a future element of an artificial division machinery in synthetic cells.

biophysics↗

bioRxiv2017

Single molecule mechanics reveal Kif15 as an active molecular ratchet with acute strain sensitivity

Human Kif15 is a tetrameric kinesin-12 that contributes critically to bipolar spindle assembly in eukaryotes. Here we examine its single molecule mechanics. Under hindering loads, Kif15 steps predominantly towards microtubule plus ends, with its forestep:backstep ratio decreasing exponentially with load and stall occurring at ~6pN. Between steps, Kif15 binds stably, usually via a single head domain. By complete contrast, under assisting loads, Kif15 detaches rapidly, even in AMPPNP. Furthermore, Kif15 can autoinhibit, via an interaction requiring its C-terminus. Autoinhibited Kif15 binds microtubules nucleotide-independently, resists both hindering and assisting loads, and is further stabilized by Tpx2, which interacts with the Kif15 C-terminus. Our data reveal the mechanics of Kif15 to be extraordinarily sensitive to loading direction. When unloaded, it walks rapidly; when pulled forwards it slips and when pulled backwards it grips. We discuss the implications of this unique mechanical behaviour for the roles of Kif15 in spindle function.

cell biology↗