Biophysical Characterization of the Membrane-proximal Ectodomain of the Receptor-type Protein-tyrosine Phosphatase Phogrin

Author(s): Martin E. Noguera, Maria E. Primo, Laura N. F. Sosa, Valeria A. Risso, Edgardo Poskus, Mario R. Ermacora

Journal Name: Protein & Peptide Letters

Volume 20 , Issue 9 , 2013

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The receptor-type protein-tyrosine phosphatase (RPTP) phogrin is localized at the membrane of secretory granules of pancreatic islet β-cells and, similarly to the closely related ICA512, plays a role in the regulation of insulin secretion, in ensuring proper granulogenesis and stability, and in the regulation of β-cell growth. The mature membraneproximal ectodomain of phogrin (MPE phogrin) was produced as a recombinant protein and characterized. CD, fluorescence, controlled proteolysis, size-exclusion chromatography, and multi-angle light scattering showed that it is a properlyfolded monomeric domain. Equilibrium experiments, in the presence of guanidinium chloride and thermal unfolding, suggest a two-state mechanism with a ΔG of 2.3-3.3 kcal/mol, respectively. The study establishes common features and differences of MPE phogrin and the homologous ectodomain of ICA512. A homology model of phogrin was built based in the x-ray structure of MPE ICA512. The model is a starting point for modeling the entire receptor and for testing the quaternary structure and interactions of this protein in vivo. A description of the membrane insertion mode and putative interacting surfaces of this large protein is fundamental for the understanding of its biological function.

Keywords: Diabetes, equilibrium unfolding, homology modeling, phogrin, receptor-type protein-tyrosine phosphatase, secretory granule.

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Article Details

Year: 2013
Page: [1009 - 1017]
Pages: 9
DOI: 10.2174/0929866511320090007
Price: $65

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