Molecular Insights and Functional Implication of LRRK2 Dimerization

Adv Neurobiol. 2017:14:107-121. doi: 10.1007/978-3-319-49969-7_6.

Abstract

The Parkinson's disease protein leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein with an enzymatic core comprising serine-threonine kinase and GTPase activities and a number of protein-protein interaction domains. While the complex domain architecture of LRRK2 has hampered its structural investigation, there is convincing evidence that LRRK2 can form dimers in solution and in the cell and that the GTPase/ROC domain plays a central role in this process. This chapter focuses on recent studies addressing the molecular nature, the functional significance, and the pathological implication of LRRK2 dimerization.

Keywords: Dimerization; GTPase; Inhibitor; Kinase; LRRK2; Phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • GTP Phosphohydrolases / chemistry
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / chemistry*
  • Mutation
  • Parkinson Disease
  • Protein Multimerization / physiology*

Substances

  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • GTP Phosphohydrolases