1bu9: Difference between revisions
New page: left|200px<br /> <applet load="1bu9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bu9" /> '''SOLUTION STRUCTURE OF P18-INK4C, 21 STRUCTU... |
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[[Image:1bu9.gif|left|200px]]<br /> | [[Image:1bu9.gif|left|200px]]<br /><applet load="1bu9" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''SOLUTION STRUCTURE OF P18-INK4C, 21 STRUCTURES'''<br /> | '''SOLUTION STRUCTURE OF P18-INK4C, 21 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
Since the structures of several ankyrin-repeat proteins including the INK4 | Since the structures of several ankyrin-repeat proteins including the INK4 (inhibitor of cyclin-dependent kinase 4) family have been reported recently, the detailed structures and the functional roles of the loops have drawn considerable interest. This paper addresses the potential importance of the loops of ankyrin-repeat proteins in three aspects. First, the solution structure of p18INK4C was determined by NMR, and the loop structures were analyzed in detail. The loops adapt nascent antiparallel beta-sheet structures, but the positions are slightly different from those in the crystal structure. A detailed comparison between the solution structures of p16 and p18 has also been presented. The determination of the p18 solution structure made such detailed comparisons possible for the first time. Second, the [1H,15N]HSQC NMR experiment was used to probe the interactions between p18INK4C and other proteins. The results suggest that p18INK4C interacts very weakly with dna K and glutathione S-transferase via the loops. The third aspect employed site-specific mutagenesis and functional assays. Three mutants of p18 and 11 mutants of p16 were constructed to test functional importance of loops and helices. The results suggest that loop 2 is likely to be part of the recognition surface of p18INK4C or p16INK4A for CDK4, and they provide quantitative functional contributions of specific residues. Overall, our results enhance understanding of the structural and functional roles of the loops in INK4 tumor suppressors in particular and in ankyrin-repeat proteins in general. | ||
==About this Structure== | ==About this Structure== | ||
1BU9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1BU9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BU9 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Byeon, I | [[Category: Byeon, I J.L.]] | ||
[[Category: Li, J.]] | [[Category: Li, J.]] | ||
[[Category: Tsai, M | [[Category: Tsai, M D.]] | ||
[[Category: cell cycle inhibitor]] | [[Category: cell cycle inhibitor]] | ||
[[Category: cyclin-dependent kinase]] | [[Category: cyclin-dependent kinase]] | ||
| Line 23: | Line 22: | ||
[[Category: tumor]] | [[Category: tumor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:59:10 2008'' | ||
Revision as of 12:59, 21 February 2008
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SOLUTION STRUCTURE OF P18-INK4C, 21 STRUCTURES
OverviewOverview
Since the structures of several ankyrin-repeat proteins including the INK4 (inhibitor of cyclin-dependent kinase 4) family have been reported recently, the detailed structures and the functional roles of the loops have drawn considerable interest. This paper addresses the potential importance of the loops of ankyrin-repeat proteins in three aspects. First, the solution structure of p18INK4C was determined by NMR, and the loop structures were analyzed in detail. The loops adapt nascent antiparallel beta-sheet structures, but the positions are slightly different from those in the crystal structure. A detailed comparison between the solution structures of p16 and p18 has also been presented. The determination of the p18 solution structure made such detailed comparisons possible for the first time. Second, the [1H,15N]HSQC NMR experiment was used to probe the interactions between p18INK4C and other proteins. The results suggest that p18INK4C interacts very weakly with dna K and glutathione S-transferase via the loops. The third aspect employed site-specific mutagenesis and functional assays. Three mutants of p18 and 11 mutants of p16 were constructed to test functional importance of loops and helices. The results suggest that loop 2 is likely to be part of the recognition surface of p18INK4C or p16INK4A for CDK4, and they provide quantitative functional contributions of specific residues. Overall, our results enhance understanding of the structural and functional roles of the loops in INK4 tumor suppressors in particular and in ankyrin-repeat proteins in general.
About this StructureAbout this Structure
1BU9 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Tumor suppressor INK4: determination of the solution structure of p18INK4C and demonstration of the functional significance of loops in p18INK4C and p16INK4A., Li J, Byeon IJ, Ericson K, Poi MJ, O'Maille P, Selby T, Tsai MD, Biochemistry. 1999 Mar 9;38(10):2930-40. PMID:10074345
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