MISC

2004年3月

Solution structure of the SEA domain from the murine homologue of ovarian cancer antigen CA125 (MUC16)

JOURNAL OF BIOLOGICAL CHEMISTRY
  • T Maeda
  • M Inoue
  • S Koshiba
  • T Yabuki
  • M Aoki
  • E Nunokawa
  • E Seki
  • T Matsuda
  • Y Motoda
  • A Kobayashi
  • F Hiroyasu
  • M Shirouzu
  • T Terada
  • N Hayami
  • Y Ishizuka
  • N Shinya
  • A Tatsuguchi
  • M Yoshida
  • H Hirota
  • Y Matsuo
  • K Tani
  • T Arakawa
  • P Carninci
  • J Kawai
  • Y Hayashizaki
  • T Kigawa
  • S Yokoyama
  • 全て表示

279
13
開始ページ
13174
終了ページ
13182
記述言語
英語
掲載種別
DOI
10.1074/jbc.M309417200
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

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.

リンク情報
DOI
https://doi.org/10.1074/jbc.M309417200
CiNii Articles
http://ci.nii.ac.jp/naid/80016583251
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/14764598
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000220334900139&DestApp=WOS_CPL
ID情報
  • DOI : 10.1074/jbc.M309417200
  • ISSN : 0021-9258
  • CiNii Articles ID : 80016583251
  • PubMed ID : 14764598
  • Web of Science ID : WOS:000220334900139

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