Marta M. Sanz Murillo

This paper elucidates the structural mechanisms by which LRRK2 is activated and autoinhibited, showing how mutations affect these processes and suggesting therapeutic strategies.

This study uses cryo-EM to reveal a two-step mechanism of RNA polymerase I stalling at abasic DNA lesions, distinct from other lesion types.

Hybrid type-II inhibitors RN277 and RN341 target inactive LRRK2 with far fewer kinase off-targets than Rebastinib, preserve S935 phosphorylation, and rescue kinesin motility in vitro.

This study uses cryo-ET to show that LRRK2 can form microtubule-bound filaments in its autoinhibited state, with structural differences compared to active-LRRK2 filaments.