Oligomerization interfaces of the mature ectodomain of the protein tyrosine phosphatase receptor IA-2

PRIMO MARÍA EVANGELINA; RISSO VALERIA A.; L.N.F. SOSA; NOGUERA MARTÍN EZEQUIEL; POSKUS EDGARDO; ERMÁCORA MARIO ROBERTO

Congreso; XXXIX Annual Meeting of Argentinean Biophysical Society SAB 2010, workshop CeBEM, structural biology in Latin America, 3rd Latin American Protein Society Meeting; 2010

IA-2 is a protein tyrosine phosphatase receptor (PTPR) located in the membrane of secretory granules (SGs) of neuroendocrine cells, and it is associated with regulatorymechanisms of protein secretion processes1. It is known that the receptor dimerizationis involved in the regulation of the secretion. Previously, we solved the structure of themature ectodomain of IA-2 (meIA-2) and identified potential dimerization interfaces2.Now, we set to study meIA-2 dimerization in solution. To address this question, mutantswere designed to disrupt the potential surface interaction. The comparative analysis ofthe mutant proteins with the wild type protein by size exclusion chromatography, circulardichroism, fluorescence and light scattering showed that meIA-2 interacts in solution bytwo interfaces resulting in equilibria of monomers, dimers and tetramers. The implicationsof these findings for biological activity will be discussed.