6f7o
NMR structure of an Odin-Sam1 stapled peptide
Structural highlights
FunctionANS1A_HUMAN Regulator of different signaling pathways. Regulates EPHA8 receptor tyrosine kinase signaling to control cell migration and neurite retraction (By similarity).[1] Publication Abstract from PubMedSam (Sterile alpha motif) domains represent small helical protein-protein interaction modules which play versatile functions in different cellular processes. The Sam domain from the EphA2 receptor binds the Sam domain of the lipid phosphatase Ship2 and this interaction modulates receptor endocytosis and degradation primarily generating pro-oncogenic effects in cell. To identify molecule antagonists of the EphA2-Sam/Ship2-Sam complex with anti-cancer activity, we focused on hydrocarbon helical stapled peptides. EphA2-Sam and one of its interactors (i.e., the first Sam domain of the adaptor protein Odin) were used as model systems for peptide design. Increase in helicity in the stapled peptides, with respect to the corresponding linear/native-like regions, was proved by structural studies conducted through CD (Circular Dichroism) and NMR (Nuclear Magnetic Resonance). Interestingly, interaction assays by means of NMR, SPR (Surface Plasmon Resonance) and MST (MicroScale Thermophoresis) techniques led to the discovery of a novel ligand of Ship2-Sam. Sam domain-based stapled peptides: Structural analysis and interaction studies with the Sam domains from the EphA2 receptor and the lipid phosphatase Ship2.,Mercurio FA, Pirone L, Di Natale C, Marasco D, Pedone EM, Leone M Bioorg Chem. 2018 Jul 20;80:602-610. doi: 10.1016/j.bioorg.2018.07.013. PMID:30036816[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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