1jdh: Difference between revisions
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[[Image:1jdh.gif|left|200px]] | [[Image:1jdh.gif|left|200px]] | ||
'''CRYSTAL STRUCTURE OF BETA-CATENIN AND HTCF-4''' | {{Structure | ||
|PDB= 1jdh |SIZE=350|CAPTION= <scene name='initialview01'>1jdh</scene>, resolution 1.90Å | |||
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|LIGAND= | |||
|ACTIVITY= | |||
|GENE= | |||
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'''CRYSTAL STRUCTURE OF BETA-CATENIN AND HTCF-4''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1JDH is a [ | 1JDH is a [[Protein complex]] structure of sequences 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=1JDH OCA]. | ||
==Reference== | ==Reference== | ||
Tcf4 can specifically recognize beta-catenin using alternative conformations., Graham TA, Ferkey DM, Mao F, Kimelman D, Xu W, Nat Struct Biol. 2001 Dec;8(12):1048-52. PMID:[http:// | Tcf4 can specifically recognize beta-catenin using alternative conformations., Graham TA, Ferkey DM, Mao F, Kimelman D, Xu W, Nat Struct Biol. 2001 Dec;8(12):1048-52. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11713475 11713475] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: tcf4]] | [[Category: tcf4]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:01:58 2008'' | ||
Revision as of 13:01, 20 March 2008
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CRYSTAL STRUCTURE OF BETA-CATENIN AND HTCF-4
OverviewOverview
Accumulation of the Wnt pathway effector beta-catenin is a hallmark of a number of cancers, including colon cancer. As beta-catenin accumulates in the cell, it forms a complex with Tcf family transcription factors and activates the transcription of several critical genes involved in cell proliferation. Because Tcf4 is the predominant Tcf factor present in colon cancer cells, drugs that specifically disrupt the beta-catenin-Tcf4 complex could be useful in treating colon cancers. Earlier structural and biochemical studies demonstrated that the central region of the beta-catenin binding domain of Tcf is essential for anchoring Tcf to beta-catenin via two conserved lysines in beta-catenin (called the charged 'buttons'). Here we report the crystal structure of a beta-catenin-Tcf4 complex at 2.0 A resolution. Our structural and mutagenesis studies show that Tcf4 docks specifically to beta-catenin using several distinct conformations in its essential central region. These conformations allow different glutamate residues in the central region of Tcf4 to form a salt bridge with the same critical charged button, Lys 312 of beta-catenin. We propose that this interaction may be the first event in beta-catenin-Tcf4 recognition.
DiseaseDisease
Known diseases associated with this structure: Colorectal cancer OMIM:[116806], Diabetes mellitus, type 2, susceptibility to OMIM:[602228], Hepatoblastoma OMIM:[116806], Hepatocellular carcinoma OMIM:[116806], Ovarian carcinoma, endometrioid type OMIM:[116806], Pilomatricoma OMIM:[116806], Pitt-Hopkins syndrome OMIM:[602272]
About this StructureAbout this Structure
1JDH is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Tcf4 can specifically recognize beta-catenin using alternative conformations., Graham TA, Ferkey DM, Mao F, Kimelman D, Xu W, Nat Struct Biol. 2001 Dec;8(12):1048-52. PMID:11713475
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