Structural analysis of the complex of F-actin and DNGR-1 by CryoEM.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25711010
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Biophysics
• Research Institution: Osaka University (2015); Institute of Physical and Chemical Research
• Principal Investigator: FUJII Takashi 大阪大学, 生命機能研究科, 招へい研究員 (10582611)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: クライオ電子顕微鏡 / アクチン繊維 / DNGR-1 / 自然免疫

Outline of Final Research Achievements

DNGR-1 is a C-type lectin receptor that binds F-actin exposed by dying cells and facilitates cross-presentation of dead cell-associated antigens by dendritic cells. We revealed the structure of DNGR-1 bound to F-actin at 7.7 angstrom resolution by CryoEM. The DNGR-1 ligand binding domain contacts three actin subunits helically arranged in the actin filament, bridging over two protofilaments. Mutation of residues predicted to mediate ligand binding led to loss of DNGR-1-dependent cross-presentation of dead cell-associated antigens, formally demonstrating that the latter depends on F-actin recognition. DNGR-1 has relatively modest affinity for F-actin but multivalent interactions allow a marked increase in binding strength. Our findings shed light on modes of actin binding by cellular proteins and reveal how extracellular detection of cytoskeletal components by dedicated receptors allows immune monitoring of loss of cellular integrity.

Free Research Field

生物物理