LRRK2 Quaternary Structure Influences Enzymatic Activity

My poster at SFN:

Poster Session 342, Parkinson's Disease: Cells and Mechanisms II, which will be held on Monday, November 17, 2008 in the Washington Convention Center: Hall A-C. The session will begin at 8:00am

Abstract Title: LRRK2 quaternary structure influences enzymatic activity
Presentation Number: 342.6
Presentation Time: 9:00am - 10:00am
Poster Board Number: Q1

Abstract

The leucine-rich repeat kinase 2 (LRRK2) protein, as part of a ‘druggable’ class of proteins, represents a viable target for therapeutic modulation in Parkinson’s disease through the identification of small molecule kinase inhibitors. Mutations in the LRRK2 gene cause late-onset Parkinson’s disease clinically and neurochemically indistinguishable from typical idiopathic disease. In cells, we find that LRRK2 protein forms complex higher order conformations. Herein, we investigate the relationship between the oligomeric forms of the protein in the disease-associated mutants as compared to the wild-type protein. We genetically and pharmacologically dissect the effect of higher-order LRRK2 structures on kinase activity and neurotoxicity. Our results show that quaternary structure confirmations critically influence LRRK2 activity in cells.

Phosphorylation of LRRK2: Functional characterization

The poster in SFN on the above topic by G. Ito et al talks about the N-terminal Serine residues (Ser 910 and Ser 973). The authors claimed in the abstract that mutating these residues did not alter the Kinase of GTPase activity of the protein. What it appears to me that these residues might not be the ones which governs the Kinase or GTPase activity in PD-related patients. I will look forward for more results in the meeting.