IDEHU   05542
INSTITUTO DE ESTUDIOS DE LA INMUNIDAD HUMORAL PROF. RICARDO A. MARGNI
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Structure of the extracelular, membrane- proximal domain of human receptor-tipe protein-tyrosine phosphatase
Autor/es:
PRIMO ME, KLINKE S, SICA MP, GOLDBAUM FA, POSKUS E, ERMÁCORA MR
Lugar:
Montevideo, Uruguay
Reunión:
Congreso; 34th Annual Meeting; 2007
Institución organizadora:
The Argentinean Biophysical Society
Resumen:
The 106‑kDa human receptor-type protein‑tyrosine phosphatase (PTPRN) is located in the membrane of secretory granules of neural, pituitary and pancreatic islet cells. Nowadays, a considerable attention is given to this membrane protein because is related to autoimmune diabetes, a pandemic disease. Its post‑translational processing yields a mature, membrane‑proximal, extracellular domain (EMP‑PTPRN) attached to the naturally inactive intracellular domain (IC‑PTPRN) through a single transmembrane region (TM‑PTPRN) [1,2]. We recently cloned and characterized EMP‑PTPRN and reported that it is an autonomous folding unit [3]. Now, we report the crystallization and preliminary X‑ray diffraction data for this fragment. EMP‑PTPRN crystallizes as a two‑fold‑axis related dimer. The lengths of the main axis of the monomer are 18.5, 14.4, and 11.6 Å. The corresponding values for the dimer are 30.5, 21.5, and 18.3 Å. The monomer fold establishes for the first time that EMP‑PTPRN is structurally related to the SEA domains (Pfam entry PF01390) found in other extracellular portions of heavily glycosilated membrane proteins and receptors. That of EMP‑PTPRN is the first crystal structure of a SEA domain. The only two previously available structures for this kind of proteins were obtained by NMR and lack sufficient details to establish the quaternary organization of the protein. The new information may help to reclassify PTPRN and to infer a biological function for its extracellular moiety, which is an enigma.