6F7N

NMR structure of EphA2-Sam stapled peptides (S13STshort)

Summary for 6F7N

• Entry DOI: 10.2210/pdb6f7n/pdb
• Related: 6F7M 6F7O
• NMR Information: BMRB: 34214
• Descriptor: Ephrin type-A receptor 2 (1 entity in total)
• Functional Keywords: ephrin receptor, sam domain, stapled peptide, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 1578.00

Authors

Mercurio, F.A.,Leone, M. (deposition date: 2017-12-11, release date: 2018-08-01, Last modification date: 2024-11-20)

Primary citation

Mercurio, F.A.,Pirone, L.,Di Natale, C.,Marasco, D.,Pedone, E.M.,Leone, M.
Sam domain-based stapled peptides: Structural analysis and interaction studies with the Sam domains from the EphA2 receptor and the lipid phosphatase Ship2.
Bioorg. Chem., 80:602-610, 2018

PubMed Abstract: Sam (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.

PubMed: 30036816
DOI: 10.1016/j.bioorg.2018.07.013

Experimental method

SOLUTION NMR