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Catalog
ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
Article
Structural Biology of LRRK2 and its Interaction with Microtubules
Review: This review focuses on new insights into the stucture of LRRK2’s cytosolic and microtubule-bound forms and challenges going forward.
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Article
Structural basis for Parkinson’s Disease-linked LRRK2’s binding to microtubules
Preprint: LRRK2 mutations are a common cause of familial PD. In some circumstances, LRRK2 co-localizes with microtubules. The authors report a cryo-electron microscopy structure of the catalytic half of LRRK2, containing its kinase (closed conformation) and GTPase domains, bound to microtubules. Further, they identified amino acids that mediate microtubule binding.
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PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074, and Thr1075) within the CORB GTPase domain
Leucine-rich-repeat-kinase 1 (LRRK1) and its homologue LRRK2 are multidomain kinases possessing a ROC-CORA-CORB containing GTPase domain and phosphorylate distinct Rab proteins. LRRK1 loss of function mutations cause the bone disorder osteosclerotic metaphyseal dysplasia, whereas LRRK2 missense mutations that enhance kinase activity cause PD. Here, the authors study the mechanism controlling LRRK1 activity and reveal a novel unexpected activation mechanism. View preprint.
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A mono- and intralink filter (mi-filter) to reduce false identifications in cross-linking mass spectrometry data
The authors show that this simple and intuitive filter has a dramatic effect on different types of cross-linking data ranging from individual protein complexes over medium-complexity affinity enrichments to proteome-wide cell lysates and significantly reduces the number of false-positive identifications for inter-protein links in all these types of XL-MS data.
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Mechanism of human PINK1 activation at the TOM complex in a reconstituted system
Preprint: The authors demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These molecular findings will aid in the development of small molecule activators of PINK1 as a therapeutic strategy for PD.