X-ray structure of the mature ectodomain of phogrin

NOGUERA ME, PRIMO ME, JAKONCIC J, POSKUS E, SOLIMENA M, ERMÁCORA MR

J Struct Funct Genomics

Springer

Año: 2015 vol. 16 p. 1 - 9

Abstract Phogrin/IA-2b and ICA512/IA-2 are two paralogs receptor-typeprotein-tyrosine phosphatases (RPTP) that localize in secretory granules ofvarious neuroendocrine cells. In pancreatic islet b-cells, they participate in the regulation of insulinsecretion, ensuring proper granulogenesis, and b-cell proliferation. The role of their cytoplasmic tailhas been partially unveiled, while that of their luminal region remainsunclear. To advance the understanding of its structure?function relationship,the X-ray structure of the mature ectodomain of phogrin (ME phogrin) at pH 7.4and 4.6 has been solved at 1.95- and 2.01-A° resolution, respectively.Similarly to the ME of ICA512, ME phogrin adopts a ferredoxin-like fold: asheet of fourantiparallel b-strands packed against two a-helices. Sequence conservation among vertebrates,plants andinsects suggests that the structuralsimilarity extends to all the receptor family. Crystallized ME phogrin ismonomeric, in agreement with solution studies but in striking contrast with thebehavior of homodimeric ME ICA512.