5MY9

Crystal structure of human 14-3-3 sigma in complex with LRRK2 peptide pS935

Summary for 5MY9

• Entry DOI: 10.2210/pdb5my9/pdb
• Descriptor: 14-3-3 protein sigma, Leucine-rich repeat serine/threonine-protein kinase 2, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: 14-3-3 lrrk2 phosphorylation ppi, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: P31947; Membrane; Peripheral membrane protein: Q5S007
• Total number of polymer chains: 2
• Total formula weight: 28264.23

Authors

Stevers, L.M.,de Vries, R.M.J.M.,Ottmann, C. (deposition date: 2017-01-26, release date: 2017-03-01, Last modification date: 2024-01-17)

Primary citation

Stevers, L.M.,de Vries, R.M.,Doveston, R.G.,Milroy, L.G.,Brunsveld, L.,Ottmann, C.
Structural interface between LRRK2 and 14-3-3 protein.
Biochem. J., 474:1273-1287, 2017

PubMed Abstract: Binding of 14-3-3 proteins to leucine-rich repeat protein kinase 2 (LRRK2) is known to be impaired by many Parkinson's disease (PD)-relevant mutations. Abrogation of this interaction is connected to enhanced LRRK2 kinase activity, which in turn is implicated in increased ubiquitination of LRRK2, accumulation of LRRK2 into inclusion bodies and reduction in neurite length. Hence, the interaction between 14-3-3 and LRRK2 is of significant interest as a possible drug target for the treatment of PD. However, LRRK2 possesses multiple sites that, upon phosphorylation, can bind to 14-3-3, thus rendering the interaction relatively complex. Using biochemical assays and crystal structures, we characterize the multivalent interaction between these two proteins.

PubMed: 28202711
DOI: 10.1042/BCJ20161078

Experimental method

X-RAY DIFFRACTION (1.327 Å)