X-ray structure of the mature ectodomain of phogrin

NOGUERA, M E; PRIMO, M E; JAKONCIC, J.; SOLIMENA, M.; POSKUS, E; ERMÁCORA, M. R.

Journal of structural and functional genomics

Springer

Año: 2015 vol. 16 p. 1 - 9

1345-711X

Abstract Phogrin/IA-2b and ICA512/IA-2 are two par- alogs receptor-type protein-tyrosine phosphatases (RPTP) that localize in secretory granules of various neuroendo- crine cells. In pancreatic islet b-cells, they participate in the regulation of insulin secretion, ensuring proper granulo- genesis, and b-cell proliferation. The role of their cyto- plasmic tail has been partially unveiled, while that of their luminal region remains unclear. To advance the under- standing of its structure?function relationship, the X-ray structure of the mature ectodomain of phogrin (ME pho- ̊grin) at pH 7.4 and 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: a sheet of four antiparallel b-strands packed against two a-helices. Sequence conservation among vertebrates, plants and insects suggests that the structural similarity extends to all the receptor family. Crystallized ME phogrin is mono- meric, in agreement with solution studies but in striking contrast with the behavior of homodimeric ME ICA512.