Marasco, M.; Kirkpatrick, J.P.; Carlomagno, T.: 1H, 13C, 15N chemical shift assignments of SHP2 SH2 domains in complex with PD-1 immune-tyrosine motifs. In: Biomolecular NMR Assignments 14 (2020), S. 179-188. DOI: https://doi.org/10.1007/s12104-020-09941-y
Zusammenfassung: | |
Inhibition of immune checkpoint receptor Programmed Death-1 (PD-1) via monoclonal antibodies is an established anticancer immunotherapeutic approach. This treatment has been largely successful; however, its high cost demands equally effective, more affordable alternatives. To date, the development of drugs targeting downstream players in the PD-1-dependent signaling pathway has been hampered by our poor understanding of the molecular details of the intermolecular interactions involved in the pathway. Activation of PD-1 leads to phosphorylation of two signaling motifs located in its cytoplasmic domain, the immune tyrosine inhibitory motif (ITIM) and immune tyrosine switch motif (ITSM), which recruit and activate protein tyrosine phosphatase SHP2. This interaction is mediated by the two Src homology 2 (SH2) domains of SHP2, termed N-SH2 and C-SH2, which recognize phosphotyrosines pY223 and pY248 of ITIM and ITSM, respectively. SHP2 then propagates the inhibitory signal, ultimately leading to suppression of T cell functionality. In order to facilitate mechanistic structural studies of this signaling pathway, we report the resonance assignments of the complexes formed by the signaling motifs of PD-1 and the SH2 domains of SHP2. © 2020, The Author(s). | |
Lizenzbestimmungen: | CC BY 4.0 Unported |
Publikationstyp: | Article |
Publikationsstatus: | publishedVersion |
Erstveröffentlichung: | 2020 |
Die Publikation erscheint in Sammlung(en): | Naturwissenschaftliche Fakultät |
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