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1ivz

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1ivz

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Solution structure of the SEA domain from murine hypothetical protein homologous to human mucin 16

Overview

Human CA125, encoded by the MUC16 gene, is an ovarian cancer antigen, widely used for a serum assay. Its extracellular region consists of tandem, repeats of SEA domains. In this study we determined the three-dimensional, structure of the SEA domain from the murine MUC16 homologue using, multidimensional NMR spectroscopy. The domain forms a unique alpha/beta, sandwich fold composed of two alpha helices and four antiparallel beta, strands and has a characteristic turn named the TY-turn between alpha1 and, alpha2. The internal mobility of the main chain is low throughout the, domain. The residues that form the hydrophobic core and the TY-turn are, fully conserved in all SEA domain sequences, indicating that the fold is, common in the family. Interestingly, no other residues are conserved, throughout the family. Thus, the sequence alignment of the SEA domain, family was refined on the basis of the three-dimensional structure, which, allowed us to classify the SEA domains into several subfamilies. The, residues on the surface differ between these subfamilies, suggesting that, each subfamily has a different function. In the MUC16 SEA domains, the, conserved surface residues, Asn-10, Thr-12, Arg-63, Asp-75, Asp-112, Ser-115, and Phe-117, are clustered on the beta sheet surface, which may, be functionally important. The putative epitope (residues 58-77) for, anti-MUC16 antibodies is located around the beta2 and beta3 strands. On, the other hand the tissue tumor marker MUC1 has a SEA domain belonging to, another subfamily, and its GSVVV motif for proteolytic cleavage is located, in the short loop connecting beta2 and beta3.

About this Structure

1IVZ is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

Solution structure of the SEA domain from the murine homologue of ovarian cancer antigen CA125 (MUC16)., Maeda T, Inoue M, Koshiba S, Yabuki T, Aoki M, Nunokawa E, Seki E, Matsuda T, Motoda Y, Kobayashi A, Hiroyasu F, Shirouzu M, Terada T, Hayami N, Ishizuka Y, Shinya N, Tatsuguchi A, Yoshida M, Hirota H, Matsuo Y, Tani K, Arakawa T, Carninci P, Kawai J, Hayashizaki Y, Kigawa T, Yokoyama S, J Biol Chem. 2004 Mar 26;279(13):13174-82. Epub 2004 Feb 4. PMID:14764598

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