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1. Signal reception in brains and neuronal systems

Higher order brain functions depend on the accurate positioning of neurons that warrant sophisticated network of information processing. Many extracellular ligands and their cell surface receptors are central to the neuronal migration and adhesion behavior, and thus are the targets for our researches.

Reelin, a gigantic glycoprotein essential
for the brain development 
Structural analyses of neuronal guidance molecules
F-spondin and semaphorins
PNAS2007 EMBOJ2006

ACTA CRYST A 2008 Nature 2010
Crystallographic and EM analysis of synaptic cell adhesion machinery
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2. Structure and function of lipoprotein receptor family proteins

Lipoprotein receptor family proteins play various biological roles other than the lipoprotein uptake. Their extracellular region has unique modular domain architecture that enables drastic conformational change, which we think is the key for the regulated ligand capture/release.

・Role of LRP6 in
the Wnt signal pathwayJImmunolMeth2009
Structural analysis of
LR11/sorLA Vps10p domain??
Mechanism of ligand recognition by LDLR class A moduleStructure2010

3. Substrate recognition mechanism of membran-associated proteases

Cell membrane is a hydrophobic barrier of cells and serves as the interface to the outside world. Proteolytic reactions that take place near this unique environment are another focus of our research. Ectodomain shedding of membrane proteins by membrane-anchored proteases such as ADAMs and the Regulated intramembrane Proteolysis (RiP) that occurs at a water-excluded hydrophobic environment are mutually related but chemically distinct type of reactions implicated in a number of biologically and medically important phenomena. Through the structural analysis, we study the substrate recognition mechanism of these membrane-anchored proteases.

RiP reaction in the E coli stress-response
Substrate recognition mechanism of gamma-secretase complex
"Exosite" recognition by ADAM family proteases