期刊
NATURE IMMUNOLOGY
卷 17, 期 5, 页码 574-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3392
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资金
- Wellcome Trust [098274/Z/12/Z, 090532/Z/09/Z, 090708/Z/09/Z]
- UK Medical Research Council [G0700232]
- Royal Society [UF120277]
- Cancer Research UK [C20724/A14414, C375/A10976]
- Wellcome Trust Centre for Human Genetics, Wellcome Trust Core Award [090532/Z/09/Z]
- Instruct, an ESFRI Landmark Project
- Wellcome Trust JIF award [060208/Z/00/Z]
- MRC [MR/L009609/1, G0900084, MR/M000141/1, G9900061, MC_UU_12010/4, G0700232, MR/L017776/1] Funding Source: UKRI
- Wellcome Trust [098274/Z/12/Z, 090708/Z/09/Z] Funding Source: Wellcome Trust
- Cancer Research UK [10976, 14414] Funding Source: researchfish
- Medical Research Council [G9900061, MR/L017776/1, MR/M000141/1, MC_UU_12010/4, G0900084, MR/L009609/1, G0700232] Funding Source: researchfish
It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell antigen receptor (TCR) triggering, but how such segregation occurs and whether it can initiate signaling is unclear. Using structural and biophysical analysis, we show that the extracellular region of CD45 is rigid and extends beyond the distance spanned by TCR-ligand complexes, implying that sites of TCR-ligand engagement would sterically exclude CD45. We also show that the formation of 'close contacts', new structures characterized by spontaneous CD45 and kinase segregation at the submicron-scale, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the potent signaling effects of, local CD45 and kinase segregation. TCR ligands have the potential to heighten signaling simply by holding receptors in close contacts.
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