[NMR paper] CD and NMR conformational studies of a peptide encompassing the Mid Loop interface of Ship2-Sam.

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CD and NMR conformational studies of a peptide encompassing the Mid Loop interface of Ship2-Sam.

Related Articles CD and NMR conformational studies of a peptide encompassing the Mid Loop interface of Ship2-Sam.

Biopolymers. 2014 May 31;

Authors: Mercurio FA, Scognamiglio PL, Di Natale C, Marasco D, Pellecchia M, Leone M

Abstract
The lipid phosphatase Ship2 is a protein that intervenes in several diseases such as diabetes, cancer, neurodegeneration, and atherosclerosis. It is made up of a catalytic domain and several protein docking modules such as a C-terminal Sam (Sterile alpha motif) domain. The Sam domain of Ship2 (Ship2-Sam) binds to the Sam domains of the EphA2 receptor (EphA2-Sam) and the PI3K effector protein Arap3 (Arap3-Sam). These heterotypic Sam-Sam interactions occur through formation of dimers presenting the canonical "Mid Loop/End Helix" binding mode. The central region of Ship2-Sam, spanning the C-terminal end of ?2, the ?3 and ?4 helices together with the ?2?3 and ?3?4 inter-helical loops, forms the Mid Loop surface that is needed to bind partners Sam domains.A peptide encompassing most of the Ship2-Sam Mid Loop interface capable of binding to both EphA2-Sam and Arap3-Sam, was previously identified. Here we investigated the conformational features of this peptide, through solution CD and NMR studies in different conditions. These studies reveal that the peptide is highly flexible in aqueous buffer, while it adopts a helical conformation in presence of 2,2,2-trifluoroethanol. The discovered structural insights and in particular the identification of a helical motif, may lead to the design of more constrained and possibly cell permeable Shiptide-analogues that could work as efficient antagonists of Ship2-Sam heterotypic interactions and embrace therapeutic applications.


PMID: 24889333 [PubMed - as supplied by publisher]



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