3j82
From Proteopedia
Electron cryo-microscopy of DNGR-1 in complex with F-actin
Structural highlights
FunctionCLC9A_MOUSE Functions as an endocytic receptor on a small subset of myeloid cells specialized for the uptake and processing of material from dead cells. Recognizes filamentous form of actin in association with particular actin-binding domains of cytoskeletal proteins, including spectrin, exposed when cell membranes are damaged, and mediate the cross-presentation of dead-cell associated antigens in a Syk-dependent manner.[1] [2] [3] [4] Publication Abstract from PubMedDNGR-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. Here we present the structure of DNGR-1 bound to F-actin at 7.7 A resolution. Unusually for F-actin binding proteins, the DNGR-1 ligand binding domain contacts three actin subunits helically arranged in the actin filament, bridging over two protofilaments, as well as two neighboring actin subunits along one protofilament. 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. Notably, 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. Structure of the Complex of F-Actin and DNGR-1, a C-Type Lectin Receptor Involved in Dendritic Cell Cross-Presentation of Dead Cell-Associated Antigens.,Hanc P, Fujii T, Iborra S, Yamada Y, Huotari J, Schulz O, Ahrens S, Kjaer S, Way M, Sancho D, Namba K, Reis e Sousa C Immunity. 2015 May 19;42(5):839-849. doi: 10.1016/j.immuni.2015.04.009. Epub 2015, May 12. PMID:25979418[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Mus musculus | Ahrens S | Fujii T | Hanc P | Huotari J | Kjaer S | Namba K | Reis e Sousa C | Schulz O | Way M | Yamada Y
