Solution structure of the first Sam domain of Odin and binding studies with the EphA2 receptor.

Biochemistry
Flavia A MercurioMarilisa Leone

Abstract

The EphA2 receptor plays key roles in many physiological and pathological events, including cancer. The process of receptor endocytosis and the consequent degradation have attracted attention as possible means of overcoming the negative outcomes of EphA2 in cancer cells and decreasing tumor malignancy. A recent study indicates that Sam (sterile alpha motif) domains of Odin, a member of the ANKS (ankyrin repeat and sterile alpha motif domain-containing) family of proteins, are important for the regulation of EphA2 endocytosis. Odin contains two tandem Sam domains (Odin-Sam1 and -Sam2). Herein, we report on the nuclear magnetic resonance (NMR) solution structure of Odin-Sam1; through a variety of assays (employing NMR, surface plasmon resonance, and isothermal titration calorimetry techniques), we clearly demonstrate that Odin-Sam1 binds to the Sam domain of EphA2 in the low micromolar range. NMR chemical shift perturbation experiments and molecular modeling studies point out that the two Sam domains interact with a head-to-tail topology characteristic of several Sam-Sam complexes. This binding mode is similar to that we have previously proposed for the association between the Sam domains of the lipid phosphatase Ship2 and EphA2....Continue Reading

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Citations

Jul 5, 2013·PloS One·Jiefei TongMichael F Moran
Dec 15, 2012·Chembiochem : a European Journal of Chemical Biology·Flavia A MercurioMarilisa Leone
Jun 30, 2015·Chembiochem : a European Journal of Chemical Biology·Flavia A MercurioMarilisa Leone
Jul 19, 2014·Archives of Biochemistry and Biophysics·José L Neira
Jun 22, 2016·Protein Science : a Publication of the Protein Society·Paul A DaRosaRachel E Klevit
Oct 21, 2016·Chembiochem : a European Journal of Chemical Biology·Flavia A MercurioMarilisa Leone
Feb 16, 2019·Current Protein & Peptide Science·Marian VincenziMarilisa Leone
Sep 21, 2019·Chembiochem : a European Journal of Chemical Biology·Flavia A MercurioMarilisa Leone
Oct 12, 2018·Current Medicinal Chemistry·Marian VincenziMarilisa Leone
Dec 7, 2019·The Journal of Biological Chemistry·Rakesh JoshiShawn S C Li
Apr 20, 2021·Biochimica Et Biophysica Acta. General Subjects·José L NeiraAdrián Velázquez-Campoy

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