bioRxivJClub
Allosteric Biosensors Unravel GTPase-Effector Feedback
bioRxiv · · Preprint · Open access
Choi, Ravishankar + 7 more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
AlloRac1 and AlloCdc42 biosensors report activity-dependent GTPase conformations without blocking effector binding, revealing Rac1 positive feedback linked to Pak1 and β-Pix.
- Why it matters: Existing in vivo GTPase conformation biosensors use reagents that block downstream binding, creating dominant negative effects and distorting normal cell physiology.
- What they did: The authors designed circularly permuted fluorescent protein insertions into conserved loops allosterically connected to effector binding sites, then imaged Rac1 activation and its localization/kinetics.
- The result: Effector interactions increased Rac1 activation, and this feedback regulated Rac1 kinetics and localization, including Rac1 activity gradients controlling motility, enabling quantitative imaging of GTPase spatio-temporal dynamics.
The findingWhy it mattersWhat they didThe result
- Open access