Localization and Structure of the Ankyrin-binding Site on 2-Spectrin

Department of Cell Biology and Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 03/2009; 284(11):6982-7. DOI: 10.1074/jbc.M809245200
Source: PubMed


Spectrins are tetrameric actin-cross-linking proteins that form an elastic network, termed the membrane skeleton, on the cytoplasmic surface of cellular membranes. At the plasma membrane, the membrane skeleton provides essential support, preventing loss of membrane material to environmental shear stresses. The skeleton also controls the location, abundance, and activity of membrane proteins that are critical to cell and tissue function. The ability of the skeleton to modulate membrane stability and function requires adaptor proteins that bind the skeleton to membranes. The principal adaptors are the ankyrin proteins, which bind to the beta-subunit of spectrin and to the cytoplasmic domains of numerous integral membrane proteins. Here, we present the crystal structure of the ankyrin-binding domain of human beta2-spectrin at 1.95 A resolution together with mutagenesis data identifying the binding surface for ankyrins on beta2-spectrin.

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Available from: Diana R. Tomchick, Aug 26, 2014
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    • "Not surprisingly, the I-TASSER threading procedure identified spectrin repeats as the best structural templates for all the tandem repeats, specifically 1CUN (chicken-brain -spectrin repeat R16-17) (Grum et al., 1999), 1U4Q (chicken-brain -spectrin repeat R15-17) (Kusunoki et al., 2004b), 1S35 (erythroid β-spectrin R8-9) (Kusunoki et al., 2004a), 3EDV (β2-spectrin repeat R14-16) (Davis et al., 2009) and 1F57 (erythrocyte ß-spectrin R14-15) (Ipsaro et al., 2009). As shown above, the identity score was very low, ranging between 0.08 and 0.18. "
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    ABSTRACT: The spectrin superfamily is composed of proteins involved in cytolinker functions. Their main structural feature is a large central subdomain with numerous repeats folded in triple helical coiled-coils. Their similarity of sequence was considered to be low without detailed quantification of the intra- and intermolecular levels. Among the superfamily, we considered as essential to propose an overview of the surface properties of all the repeats of the five proteins of the spectrin family, namely α- and β-spectrins, α-actinin, dystrophin and utrophin. Therefore, the aim of this work was to obtain a quantitative comparison of all the repeats at both the primary sequence and the three-dimensional levels. For that purpose, we applied homology modelling methods to obtain structural models for successive and overlapping tandem repeats of the human erythrocyte α- and β-spectrins and utrophin, as previously undertaken for dystrophin, and we used the known structure of α-actinin. The matrix calculation of the pairwise similarities of all the repeat sequences and the electrostatic and hydrophobic surface properties throughout the protein family support the view that spectrins and α-actinin on one hand and utrophin and dystrophin on the other hand share some structural similarities, but a detailed molecular characterisation highlights substantial differences. The repeats within the family are far from identical, which is consistent with their multiple interactions with different cellular partners, including proteins and membrane lipids.
    Full-text · Article · Mar 2014 · Journal of Structural Biology
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    Full-text · Article · Mar 2013 · Journal of Experimental Medicine
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    • "Not surprisingly, the I-TASSER threading procedure identified spectrin repeats as the best templates, specifically 1U4Q (chicken-brain α-spectrin repeat R15-17) [14], 1S35 (erythroid β-spectrin R8-9) [13] and 3EDV (β2-spectrin repeat R14-16) [15]. As expected for spectrin-like repeats, the identity score was low, ranging between 0.08 and 0.18. "
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