2013 Fiscal Year Final Research Report

Structural basis for C-type lectin receptor in innate immunity

Research Project

Project/Area Number	24770111
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Structural biochemistry
Research Institution	Institute of Physical and Chemical Research
Principal Investigator	NAGAE Masamichi 独立行政法人理化学研究所, 糖鎖構造生物学研究チーム, 研究員 (60619873)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	X線結晶構造解析 / 生物物理
Research Abstract	The immune system is a system which discriminates and removes the pathogens and highly developed in mammals. Groups of pathogens share similar chemical structures known as pathogen-associated molecular pathogens (PAMPs). Many cell-surface receptors which involve in innate immunity specifically recognize PAMPs. Especially, C-type lectin receptors (CTLR) bind to carbohydrates derived from pathogens such as bacteria, virus and fungi. Both DCIR-2 and BDCA-2 belong to CTLRs and are highly expressed on dendritic cells. DCIR-2 works as negative regulator, while BDCA-2 works as activator. Our purpose is to clarify the ligand recognition of both proteins. We initially determined the crystal structures of DCIR-2 in the absence and complexed with its specific ligand, bisected N-glycan. As a result, non-conserved amino acids enable DCIR-2 to bind to bisected glycan. Next we solved the crystal structure of BDCA-2 in unliganded form. BDCA-2 forms 'domain-swapped' dimer in various conditions.