View source for 1jb6

[[Image:1jb6.jpg|left|200px]]

 {{Structure
|PDB= 1jb6 |SIZE=350|CAPTION= <scene name='initialview01'>1jb6</scene>, resolution 1.70&Aring;
|SITE= 
|LIGAND= <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene>
|ACTIVITY= 
|GENE= 
|DOMAIN=
|RELATEDENTRY=[[1g39|1g39]], [[1g2y|1g2y]], [[1g2z|1g2z]], [[1f93|1f93]]
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jb6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jb6 OCA], [http://www.ebi.ac.uk/pdbsum/1jb6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jb6 RCSB]</span>
}}

'''Crystal Structure of Dimerization Domain (1-33) of HNF-1alpha'''


==Overview==
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.

==About this Structure==
1JB6 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JB6 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:[http://www.ncbi.nlm.nih.gov/pubmed/11439029 11439029]
[[Category: Single protein]]
[[Category: Hua, Q X.]]
[[Category: Narayana, N.]]
[[Category: Weiss, M A.]]
[[Category: four-helix bundle]]
[[Category: non-canonical turn]]

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