InterPro domain: IPR001715

A number of actin-binding proteins, including spectrin, alpha-actinin and fimbrin, contain a 250 amino acid stretch called the actin binding domain(ABD). The ABD has probably arisen from duplication of a domain which is also found in a single copy in a number of other proteins like calponin or the vav proto-oncogene and has been called calponin homology (CH) domain [ 1 , 2 ].

A detailed analysis of The CH domain-containing proteins has shown that they can be divided in three groups [ 3 ]:

• The fimbrin family of monomeric actin cross-linking molecules containing two ABDs
• Dimeric cross-linking proteins (alpha-actinin, beta-spectrin, filamin, etc.) and monomeric F-actin binding proteins (dystrophin, utrophin) each containing one ABD
• Proteins containing only a single amino terminal CH domain.

Each single ABD, comprising two CH domains, is able to bind one actin monomer in the filament. The N-terminal CH domain has the intrinsic ability tobind actin, albeit with lower affinity than the complete ABD, whereas the C-terminal CH bind actin extremely weakly or not at all. Neverthelessboth CH domains are required for a fully functional ABD; the C-terminal CH domain contributing to the overall stability of the complete ABD throughinter-domain helix-helix interactions [ 3 ]. Some of the proteins containing a single CH domain also bind to actin, although this has not been shown to be via the single CH domain alone [ 3 ]. In addition, the CH domain occurs also in a number of proteins not known to bind actin, a notable example being the vav protooncogene.

The resolution of the 3D structure of various CH domains has shown that the conserved core consist of four major alpha-helices [ 3 ].

Proteins containing a calponin domain include:

• Calponin, which is involved in the regulation of contractility and organisation of the actin cytoskeleton in smooth muscle cells [ 3 ].
• Beta-spectrin, a major component of a submembrane cytoskeletal network connecting actin filaments to integral plasma membrane proteins [ 4 ].
• The actin-cross-linking domain of the fimbrin/plastin family of actin filament bundling or cross-linking proteins [ 5 ].
• Utrophin,a close homologue of dystrophin [ 6 ].
• Dystrophin, the protein found to be defective in Duchenne muscular dystrophy; this protein contains a tandem repeat of two CH domains [ 6 ].
• Actin-binding domain of plectin, a large and widely expressed cytolinker protein [ 7 ].
• The N-terminal microtubule-binding domain of microtubule-associated protein eb1 (end-binding protein), a member of a conserved family of proteins that localise to the plus-ends of microtubules [ 8 ].
• Ras GTPase-activating-like protein rng2, an IQGAP protein that is essential for the assembly of an actomyosin ring during cytokinesis [ 9 ].
• Transgelin, which suppresses androgen receptor transactivation [ 10 ].

1. CH domains revisited. FEBS Lett. 431, 134-7
2. The 2.0 A structure of the second calponin homology domain from the actin-binding region of the dystrophin homologue utrophin. J. Mol. Biol. 285, 1257-64
3. Solution structure of the calponin CH domain and fitting to the 3D-helical reconstruction of F-actin:calponin. Structure 10, 249-58
4. beta-Spectrin functions independently of Ankyrin to regulate the establishment and maintenance of axon connections in the Drosophila embryonic CNS. Development 134, 273-84
5. The structure of an actin-crosslinking domain from human fimbrin. Nat. Struct. Biol. 4, 708-12
6. The structure of the N-terminal actin-binding domain of human dystrophin and how mutations in this domain may cause Duchenne or Becker muscular dystrophy. Structure 8, 481-91
7. Actin-binding domain of mouse plectin. Crystal structure and binding to vimentin. Eur. J. Biochem. 271, 1873-84
8. Crystal structure of the amino-terminal microtubule-binding domain of end-binding protein 1 (EB1). J. Biol. Chem. 278, 36430-4
9. Structure, crystal packing and molecular dynamics of the calponin-homology domain of Schizosaccharomyces pombe Rng2. Acta Crystallogr. D Biol. Crystallogr. 60, 1396-403
10. Transgelin functions as a suppressor via inhibition of ARA54-enhanced androgen receptor transactivation and prostate cancer cell growth. Mol. Endocrinol. 21, 343-58