The leucine-rich repeat kinase 2 (LRRK2) gene and α-synuclein gene (SNCA) are the key influencing factors of Parkinson’s disease (PD). It is reported that dysfunction of LRRK2 may influence the accumulation of α-synuclein and its pathology to alter cellular functions and signaling pathways by the kinase activation of LRRK2. The accumulation of α-synuclein is one of the main stimulants of microglial activation. Microglia are macrophages that reside in the brain, and acti-vation of microglia is believed to contribute to neuroinflammation and neuronal death in PD. LRRK2 is a large and complex protein combining a GTPase and protein kinase activity, and disease mutations increase the kinase activity, while presumably decreasing the GTPase activity. Although a cross-communication between both catalytic activities has been suggested, the underlying mechanisms and the regulatory role of the GTPase domain remain unknown. Recently, several structures of LRRK2 have been reported, but so far structures of Roco proteins in their activated GTP-bound state are lacking. A recent work by Galicia and coworkers, reported the cryoEM structure of a simpler bacterial Roco protein (CtRoco) in its GTP-bound state, aided by the use of two conformation-specific activating nanobodies: NbRoco1 and NbRoco2. Here you can see LRR domain of Roco protein from Chlorobaculum tepidum bound to the activating Nanobody NbRoco2 (PDB code: 8R4C)

#molecularart #parkinson #nanobody #roco #lrr #domain #activation

Structure rendered with @proteinimaging, post-processed with @stylar.ai_official and depicted with @corelphotopaint