Structural basis for Parkinson's disease-linked LRRK2's binding to microtubules.

Leucine-rich repeat kinase 2 (LRRK2) is one of the most commonly mutated genes in familial Parkinson's disease (PD). Under some circumstances, LRRK2 co-localizes with microtubules in cells, an association enhanced by PD mutations. We report a cryo-EM structure of the catalytic half of LRRK2, containing its kinase, in a closed conformation, and GTPase domains, bound to microtubules.

Distinct axial and lateral interactions within homologous filaments dictate the signaling specificity and order of the AIM2-ASC inflammasome.

Inflammasomes are filamentous signaling platforms integral to innate immunity. Currently, little is known about how these structurally similar filaments recognize and distinguish one another. A cryo-EM structure of the AIM2 filament reveals that the architecture of the upstream filament is essentially identical to that of the adaptor ASC filament.

Structure of LRRK2 in Parkinson's disease and model for microtubule interaction.

Leucine-rich repeat kinase 2 (LRRK2) is the most commonly mutated gene in familial Parkinson's disease and is also linked to its idiopathic form. LRRK2 has been proposed to function in membrane trafficking and colocalizes with microtubules. Despite the fundamental importance of LRRK2 for understanding and treating Parkinson's disease, structural information on the enzyme is limited.

Preparation of filamentous proteins for electron microscopy visualization and reconstruction.

Cryo electron microscopy (cryo-EM) has become a mainstream tool for determining the structures of macromolecular complexes at the atomic resolution. It has many advantages over other techniques such as X-ray crystallography and nuclear magnetic resonance (NMR). However, it also entails several challenges, a major one being preparation of an ideal sample.