Katja Rosti

University of Helsinki
Supervisor: Tommi Kajander
Funding: other
Date: 2012-01-01

Structure, folding and function of neuronal leucine rich repeat proteins

Repeat proteins are a large group of proteins, described by domains with short, typically 20-40 amino acids repeating motif. Among the most common ones are the leucine rich repeat (LRR), ankyrin repeats or tetratricopeptide repeats. Their most common function is to mediate the protein-protein interactions.

A large number of LRR containing proteins have recently been described with neuronal functions, such as LRRTM family and the netrin-G ligand (NGL) family, synaptic adhesion like molecules (SALMs) and the AMIGOs. Several of these share a similar overall domain structure for the extracellular part, having an N-terminal LRR domain, followed by an immunoglobulin-like domain (IG) or a fibronectin-type domain. Many of these proteins function as adhesion molecules, in particular determining the synaptic specificity and via this context they are often linked directly to cognitive disorders like schizophrenia and autism.

The focus of this work will be on the structural biology of neuronal LRR receptor proteins. I will concentrate on developing strategies for over-expression of the mammalian LRRTM proteins. Further, I will perform structural and biophysical studies on the folding of LRR-type proteins in order to understand their stability and to be able to screen suitable inhibitors and ligands.