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.
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.
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DOI：
10.1016/j.immuni.2015.04.009
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发表时间：
2015-05-19
期刊：
影响因子：
32.4
通讯作者：
Reis e Sousa, Caetano
中科院分区：
文献类型：
--
作者：
Hanc, Pavel;Fujii, Takashi;Iborra, Salvador;Yamada, Yurika;Huotari, Jatta;Schulz, Oliver;Ahrens, Susan;Kjaer, Svend;Way, Michael;Sancho, David;Namba, Keiichi;Reis e Sousa, Caetano
DNGR-1是一种C型凝集素受体，其结合由垂死细胞暴露的F-肌动蛋白，并促进树突状细胞交叉呈递死细胞相关抗原。在这里，我们提出的结构DNGR-1结合F-肌动蛋白在7.7 nm分辨率。对于F-肌动蛋白结合蛋白，DNGR-1配体结合结构域与螺旋排列在肌动蛋白丝中的三个肌动蛋白亚基接触，桥接两个原丝，以及沿沿着一个原丝的两个相邻的肌动蛋白亚基。预测介导配体结合的残基的突变导致死亡细胞相关抗原的DNGR-1依赖性交叉呈递的丧失，正式证明后者依赖于F-肌动蛋白识别。值得注意的是，DNGR-1对F-肌动蛋白具有相对适度的亲和力，但多价相互作用允许结合强度显著增加。我们的研究结果揭示了细胞蛋白结合肌动蛋白的模式，并揭示了细胞骨架成分的细胞外检测如何通过专用受体允许免疫监测细胞完整性的丧失。
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. Here we present the structure of DNGR-1 bound to F-actin at 7.7 Å 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.
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影响因子：
2.9
作者：
Abdiche, Yasmina;Malashock, Dan;Pons, Jaurne
通讯作者：
Pons, Jaurne
影响因子：
64.8
作者：
Fujii, Takashi;Iwane, Atsuko H.;Namba, Keiichi
通讯作者：
Namba, Keiichi
影响因子：
64.8
作者：
Holmes, KC;Angert, I;Schröder, RR
通讯作者：
Schröder, RR
DOI：
10.1084/jem.20092618
发表时间：
2010-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Poulin LF;Salio M;Griessinger E;Anjos-Afonso F;Craciun L;Chen JL;Keller AM;Joffre O;Zelenay S;Nye E;Le Moine A;Faure F;Donckier V;Sancho D;Cerundolo V;Bonnet D;Reis e Sousa C
通讯作者：
Reis e Sousa C
影响因子：
64.8
作者：
Kitov, PI;Sadowska, JM;Bundle, DR
通讯作者：
Bundle, DR