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| | {{STRUCTURE_1jb6| PDB=1jb6 | SCENE= }} | | {{STRUCTURE_1jb6| PDB=1jb6 | SCENE= }} |
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| - | '''Crystal Structure of Dimerization Domain (1-33) of HNF-1alpha'''
| + | ===Crystal Structure of Dimerization Domain (1-33) of HNF-1alpha=== |
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| - | ==Overview==
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| - | Maturity-onset diabetes mellitus of the young (MODY) is a human genetic syndrome most commonly due to mutations in hepatocyte nuclear factor-1alpha (HNF-1alpha). Here, we describe the crystal structure of the HNF-1alpha dimerization domain at 1.7 A resolution and assess its structural plasticity. The crystal's low solvent content (23%, v/v) leads to tight packing of peptides in the lattice. Two independent dimers, similar in structure, are formed in the unit cell by a 2-fold crystallographic symmetry axis. The dimers define a novel intertwined four-helix bundle (4HB). Each protomer contains two alpha-helices separated by a sharp non-canonical turn. Dimer-related alpha-helices form anti-parallel coiled-coils, including an N-terminal "mini-zipper" complementary in structure, symmetry and surface characteristics to transcriptional coactivator dimerization cofactor of HNF-1 (DCoH). A confluence of ten leucine side-chains (five per protomer) forms a hydrophobic core. Isotope-assisted NMR studies demonstrate that a similar intertwined dimer exists in solution. Comparison of structures obtained in multiple independent crystal forms indicates that the mini-zipper is a stable structural element, whereas the C-terminal alpha-helix can adopt a broad range of orientations. Segmental alignment of the mini-zipper (mean pairwise root-mean-square difference (rmsd) in C(alpha) coordinates of 0.29 A) is associated with a 2.1 A mean C(alpha) rmsd displacement of the C-terminal coiled-coil. The greatest C-terminal structural variation (4.1 A C(alpha) rmsd displacement) is observed in the DCoH-bound peptide. Diabetes-associated mutations perturb distinct structural features of the HNF-1alpha domain. One mutation (L12H) destabilizes the domain but preserves structural specificity. Adjoining H12 side-chains in a native-like dimer are predicted to alter the functional surface of the mini-zipper involved in DCoH recognition. The other mutation (G20R), by contrast, leads to a dimeric molten globule, as indicated by its 1H-NMR features and fluorescent binding of 1-anilino-8-naphthalene sulfonate. We propose that a glycine-specific turn configuration enables specific interactions between the mini-zipper and the C-terminal coiled-coil.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11439029}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11439029 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11439029}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Four-helix bundle]] | | [[Category: Four-helix bundle]] |
| | [[Category: Non-canonical turn]] | | [[Category: Non-canonical turn]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:00:19 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 19:57:18 2008'' |
Revision as of 16:57, 1 July 2008
Template:STRUCTURE 1jb6
Crystal Structure of Dimerization Domain (1-33) of HNF-1alpha
Template:ABSTRACT PUBMED 11439029
About this Structure
1JB6 is a Single protein structure. Full crystallographic information is available from OCA.
Reference
The dimerization domain of HNF-1alpha: structure and plasticity of an intertwined four-helix bundle with application to diabetes mellitus., Narayana N, Hua Q, Weiss MA, J Mol Biol. 2001 Jul 13;310(3):635-58. PMID:11439029
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