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

MARÍA E. PRIMO; VALERIA A. RISSO; LAURA N.F. SOSA; MARTÍN E. NOGUERA; EDGARDO POSKUS ; MARIO R. ERMÁCORA

Salta

Congreso; 3rd Latin American Protein Society Meeting; 2010

SAD, CeBEM, Latin American Protein Society

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 regulatory mechanisms of protein secretion processes1. It is known that the receptor dimerization is involved in the regulation of the secretion. Previously, we solved the structure of the mature 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, mutants were designed to disrupt the potential surface interaction. The comparative analysis of the mutant proteins with the wild type protein by size exclusion chromatography, circular dichroism, fluorescence and light scattering showed that meIA-2 interacts in solution by two interfaces resulting in equilibria of monomers, dimers and tetramers. The implications of these findings for biological activity will be discussed.