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550 a.a.
Key reference
DOI no: 10.1016/j.str.2007.12.021 Structure 16:478-487 (2008) PubMed id: 18334222
Crystal structure of a full-length beta-catenin. Y.Xing, K.Takemaru, J.Liu, J.D.Berndt, J.J.Zheng, R.T.Moon, W.Xu. ABSTRACT
beta-catenin plays essential roles in cell adhesion and Wnt signaling, while deregulation of beta-catenin is associated with multiple diseases including cancers. Here, we report the crystal structures of full-length zebrafish beta-catenin and a human beta-catenin fragment that contains both the armadillo repeat and the C-terminal domains. Our structures reveal that the N-terminal region of the C-terminal domain, a key component of the C-terminal transactivation domain, forms a long alpha helix that packs on the C-terminal end of the armadillo repeat domain, and thus forms part of the beta-catenin superhelical core. The existence of this helix redefines our view of interactions of beta-catenin with some of its critical partners, including ICAT and Chibby, which may form extensive interactions with this C-terminal domain alpha helix. Our crystallographic and NMR studies also suggest that the unstructured N-terminal and C-terminal tails interact with the ordered armadillo repeat domain in a dynamic and variable manner.
Selected figure(s)
Figure 2.
Figure 2. Interactions between β-Catenin C-Terminal Domain and Central Armadillo Repeat Domain
(A) Electrostatic surface of the β-catenin armadillo repeat domain covered by the β-catenin C-terminal domain. Residues from the armadillo repeat domain are labeled in black. β-catenin C-terminal domain is in a stick model labeled in red. Key residues of the C-terminal domain interacting with the armadillo repeat domain are highlighted in green for hydrophobic interactions and yellow for charge-charge interactions.
(B) Sequence alignment of the β-catenin C-terminal domain with CLUSTALW. Invariant residues are labeled with stars in red, strongly similar residues are labeled with (:) in green, and weakly similar residues are labeled with (.) in blue. Sequences of the C-terminal domain visible in the β-catenin-R1C crystal structure are framed. The conserved hydrophobic residues (L674, L678, and L682) that docked the helix C into the armadillo repeat domain are marked with arrows.
(C) Ligplot presentation of interactions between β-catenin residues in the C-terminal domain (purple) and the armadillo repeat domain (red). Hydrogen bonds and charge-charge interactions are designated with green dashed lines and distance in Å. A red starburst together with a red dashed line represents hydrophobic interactions.Figure 4.
Figure 4. The Role of Helix C in β-Catenin Protein-Protein Interactions
(A) Potential interactions between β-catenin helix C and ICAT. β-catenin-R1C (βcat-R1C, cyan) is superimposed onto β-catenin/ICAT (βcat/ICAT, yellow and magenta), based on the Cα's of β-catenin armadillo repeats 10–12 (residues 563–663).
(B) Helix C is unlikely to affect the interaction between the phophorylated E-cadherin and β-catenin armadillo repeats. β-catenin-R1C (βcat-R1C, cyane) is superimposed with β-catenin/phospho-Ecadherin (βcat/pEcad, yellow and red, PDB code: 1I7W) based on all twelve armadillo repeats.
(C) The helix C is required for β-catenin to interact with Chibby. Purified MBP-Chibby protein was immobilized to amylose beads; purified β-catenin and β-catenin fragments were tested for their binding to immobilized MBP-Chibby. The total input and bound β-catenin and β-catenin fragments were visualized by Western blot.The above figures are reprinted by permission from Cell Press: Structure (2008, 16, 478-487) copyright 2008. Figures were selected by an automated process.
Literature references that cite this PDB file's key reference
PubMed id Reference
19435523 A.Mofunanya, F.Q.Li, J.C.Hsieh, and K.I.Takemaru (2009).
Chibby forms a homodimer through a heptad repeat of leucine residues in its C-terminal coiled-coil motif.BMC Mol Biol, 10, 41.
19305417 C.Mosimann, G.Hausmann, and K.Basler (2009).
Beta-catenin hits chromatin: regulation of Wnt target gene activation.Nat Rev Mol Cell Biol, 10, 276-286.
19247479 H.Striegl, Y.Roske, D.Kümmel, and U.Heinemann (2009).
Unusual armadillo fold in the human general vesicular transport factor p115.PLoS ONE, 4, e4656.
PDB code: 2w3c 20066110 L.Shapiro, and W.I.Weis (2009).
Structure and biochemistry of cadherins and catenins.Cold Spring Harbor Perspect Biol, 1, a003053.
18604449 X.Chen, J.Yang, P.M.Evans, and C.Liu (2008).
Wnt signaling: the good and the bad.Acta Biochim Biophys Sin (Shanghai), 40, 577-594. The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.
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