Journal of Molecular Biology
Volume 285, Issue 3, 22 January 1999, Pages 1257-1264
Journal home page for Journal of Molecular Biology

Regular Article
The 2.0 Å Structure of the Second Calponin Homology Domain from the Actin-binding Region of the Dystrophin Homologue Utrophin,☆☆

https://doi.org/10.1006/jmbi.1998.2406Get rights and content

Abstract

Utrophin is a close homologue of dystrophin, the protein defective in Duchenne muscular dystrophy. Like dystrophin, it is composed of three regions: an N-terminal region that binds actin filaments, a large central region with triple coiled-coil repeats, and a C-terminal region that interacts with components in the dystroglycan protein complex at the plasma membrane. The N-terminal actin-binding region consists of two calponin homology domains and is related to the actin-binding domains of a superfamily of proteins including α-actinin, spectrin and fimbrin. Here, we present the 2.0 Å structure of the second calponin homology domain of utrophin solved by X-ray crystallography, and compare it to the other calponin homology domains previously determined from spectrin and fimbrin.

References (51)

  • M. Mezgueldi et al.

    Mapping of the functional domains in the amino-terminal region of calponin

    J. Biol. Chem.

    (1992)
  • T. Stradal et al.

    CH domains revisited

    FEBS Letters

    (1998)
  • S.J. Winder et al.

    Protein production in 3 different expression vectors from a single PCR product

    Anal. Biochem.

    (1995)
  • S.J. Winder et al.

    Dystrophin and utrophin the missing links

    FEBS Letters

    (1995)
  • T.K. Attwood et al.

    A colour INteractive editor for multiple alignments

    EMBnet News

    (1997)
  • G.J. Barton

    ALSCRIPT a tool to format multiple sequence alignments

    Protein Eng.

    (1993)
  • A.R. Bresnick et al.

    Identification of a short sequence essential for actin binding by Dictyostelium ABP-120

    J. Biol. Chem

    (1990)
  • A.T. Brünger

    X-plor: version 3.1. A System for X-ray Crystallography and NMR

    (1992)
  • K.P. Campbell et al.

    Association of dystrophin and an integral membrane glycoprotein

    Nature

    (1989)
  • K.D. Carugo et al.

    Crystal structure of a CH domain

    Nature Struct. Biol.

    (1997)
  • A.E. Deconinck et al.

    Postsynaptic abnormalities at the neuromuscular junctions of utrophin-deficient mice

    J. Cell Biol.

    (1997)
  • J. Devereux

    The GCG Sequence Analysis Software Package

    (1989)
  • J. Felsenstein

    PHYLIP-phylogeny inference package

    Cladistics

    (1993)
  • S.C. Goldsmith et al.

    The structure of an actin-crosslinking domain from human fimbrin

    Nature Struct. Biol.

    (1997)
  • R.M. Grady et al.

    Subtle neuromuscular defects in utrophin-deficient mice

    J. Cell Biol.

    (1997)
  • Cited by (41)

    • Synthetic actin-binding domains reveal compositional constraints for function

      2008, International Journal of Biochemistry and Cell Biology
    • Molecular architecture in muscle contractile assemblies

      2005, Advances in Protein Chemistry
      Citation Excerpt :

      The structure of the α‐actinin rod has been defined by protein crystallography (Djinovic‐Carugo et al., 1999; Ylanne et al., 2001). The actin‐binding region in α‐actinin has also been determined (Franzot et al., 2005), and is very similar to equivalent domains in dystrophin and utrophin (Keep et al., 1999). In the Z‐band, the α‐actinin molecules form cross‐links between anti‐parallel actin filaments.

    • Spectrin, α-actinin, and dystrophin

      2005, Advances in Protein Chemistry
      Citation Excerpt :

      These were the CH2 domain of spectrin (Carugo et al., 1997) and the N-terminal ABD of fimbrin, comprising two CH domains (CH1.1 and CH2.1) (Goldsmith et al., 1997). The crystal structure of the second utrophin CH domain (CH2) was later published by Keep et al. (1999a). It was not long, however, before the complete actin-binding domain of utrophin was crystallized (Keep et al., 1999b), followed closely by dystrophin (Norwood et al., 2000).

    View all citing articles on Scopus

    Abbreviations used: ABS(1-3), actin binding sequence (1 to 3); BMD, Becker muscular dystrophy; CH1, first calponin homology domain; CH2, second calponin homology domain; DMD, Duchenne muscular dystrophy

    ☆☆

    Edited by R. Huber

    f1

    Corresponding author

    f2

    E-mail address of the corresponding author: [email protected]

    View full text