1ivz
From Proteopedia
(New page: 200px<br /><applet load="1ivz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ivz" /> '''Solution structure of the SEA domain from mu...) |
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| - | [[Image:1ivz.gif|left|200px]]<br /><applet load="1ivz" size=" | + | [[Image:1ivz.gif|left|200px]]<br /><applet load="1ivz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ivz" /> | caption="1ivz" /> | ||
'''Solution structure of the SEA domain from murine hypothetical protein homologous to human mucin 16'''<br /> | '''Solution structure of the SEA domain from murine hypothetical protein homologous to human mucin 16'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human CA125, encoded by the MUC16 gene, is an ovarian cancer antigen | + | 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== | ==About this Structure== | ||
| - | 1IVZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | + | 1IVZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IVZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Kigawa, T.]] | [[Category: Kigawa, T.]] | ||
[[Category: Maeda, T.]] | [[Category: Maeda, T.]] | ||
| - | [[Category: RSGI, RIKEN | + | [[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]] |
[[Category: Yokoyama, S.]] | [[Category: Yokoyama, S.]] | ||
[[Category: mucin 16]] | [[Category: mucin 16]] | ||
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[[Category: structural genomics]] | [[Category: structural genomics]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:16:15 2008'' |
Revision as of 11:16, 21 February 2008
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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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