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Review
. 1998 Aug;9(8):1951-9.
doi: 10.1091/mbc.9.8.1951.

The ADF homology (ADF-H) domain: a highly exploited actin-binding module

P Lappalainen  1 , M M Kessels, M J Cope, D G Drubin
Affiliations
Free PMC article
Review

The ADF homology (ADF-H) domain: a highly exploited actin-binding module

P Lappalainen et al. Mol Biol Cell. 1998 Aug.
Free PMC article
No abstract available

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Figures

Figure 1
Figure 1
Domain structures of the three classes of ADF-H domain proteins. The ADF/cofilin proteins are composed of a single ADF-H domain. Twinfilins are composed of two ADF-H domains arranged in tandem. Members of the drebrin/Abp1 class have an ADF-H domain at the N-terminus of the protein, followed by a variable region and a C-terminal SH3 domain.
Figure 2
Figure 2
Sequence alignments of representative examples of ADF-H domains. This alignment was produced essentially according to the methods described for myosin motor domains by Cope et al., (1996). Briefly, the collected sequences were subjected to an initial alignment using the Clustal-W program (Thompson et al., 1994). This initial alignment was refined, thus defining a core ADF-H domain. Acidic (D and E), basic (K, R, and H), uncharged nonpolar (A, I, M, V, L, F, W, and P), and other residues (Y, T, S, G, N, Q, and C) have been colored in red, purple, green, and yellow, respectively. The residues that are >75% conserved throughout the entire ADF-H domain family are boxed. Dashes indicate positions occupied by residues from other ADF/cofilin proteins within the full alignment. The residues shown to be essential for interactions of yeast cofilin with actin (Lappalainen et al., 1997) are indicated by asterisks above the sequences, and the region that has been shown to be important for actin interactions by peptide inhibition studies (Yonezawa et al., 1989) is shown by a dashed line above the sequences. The positions of secondary structure elements based on the yeast cofilin crystal structure (Fedorov et al., 1997) and the nuclear magnetic resonance structure of human destrin (Hatanaka et al., 1996) are shown above the sequences. Protein names, database, and accession numbers for the sequences, respectively, are listed in the legend to Figure 3.
Figure 3
Figure 3
(A) An unrooted phylogenetic tree of ADF-H domains. This tree was produced by subjecting the alignment depicted in Figure 2 to analysis by the Clustal-W software package (Thompson et al., 1994). An allowance was made for multiple substitutions (Kimura, 1983). Information from intervals in the alignment for which gaps are found in some sequences was included. (Note: the tree architecture is almost identical if gaps are omitted.) The tree was tested (1000 trials) for branching order confidence by bootstrapping (Felsenstein, 1985). Filled circles indicate branch points supported beyond a confidence level of 85%. Empty circles indicate branch points supported beyond the 50% but below the 85% confidence level. Dashed lines indicate the three classes described in this essay. A bar showing 5% divergence is included. Further information on this procedure (as applied to myosin motor domains) can be found on the Worldwide Web at http://www.mrc-lmb.cam.ac.uk/. (B) A simplified, rooted tree depicting the evolution of ADF-H domain proteins in mice. All three families of ADF-H domain proteins were present in the common ancestor of yeast and animals. Distinct members of the ADF/cofilin family in mouse arose after the emergence of vertebrates. The asterisks denote our predictions that destrin- and drebrin-like proteins will be found in mouse, based on the phylogenetic tree shown in A. Protein names, database, and accession numbers for the sequences, respectively, are listed below. Where no database is stated, the accession number refers to GenBank. S. cerevisiae cofilin: Swiss-Prot, Q03048; S. pombe cofilin: DDBJ, D89939; D. discoideum cofilin: Swiss-Prot, P54706; A. castellanii actophorin: Swiss-Prot, P37167; A. thaliana ADF1: U48938; A. thaliana ADF2: U48939; L. longifolium ADF: PIR, S30935; Brassica napus ADF: PIR, S30934; Z. mays ADF1: Swiss-Prot, P46251; Z. mays ADF2: X97725; Z. mays ADF3: X97726; Triticum aestivum cofilin: U58278; Drosophila melanogaster ADF: PIR, A57569; Caenorhabditis elegans ADF1: Swiss-Prot, Q07750; C. elegans ADF2 (Swiss-Prot: Q07749), T. gondii ADF: U62146; H. sapiens destrin 2:(U47924; H. sapiens destrin 1: PIR, A54184; S. scrofa destrin: DDBJ, D90053; Gallus gallus ADF: J02912; R. norvegicus cofilin: Swiss-Prot, P45592; Mus musculus cofilin (nonmuscle isoform): Swiss-Prot, P18760; H. sapiens cofilin: EMBL, X95404; S. scrofa cofilin: M20866; G. gallus cofilin: M55659; M. musculus cofilin (muscle isoform): Swiss-Prot, P45591; X. laevis cofilin 1: U26270; X. laevis cofilin 2: Swiss-Prot, P45593; M. musculus twinfilin (repeat-1): U82324; H. sapiens twinfilin (repeat-1): PIR, A55922; S. cerevisiae twinfilin (repeat-1): SGD, YGR080W; M. musculus twinfilin (repeat-2): U82324; H. sapiens twinfilin (repeat-2): PIR, 55922; S. cerevisiae twinfilin (repeat-2): SGD, YGR080W; H. sapiens drebrin E: Swiss-Prot, Q16643; R. norvegicus drebrin A: Swiss-Prot, Q07266; G. gallus drebrin A, E1 and E2: Swiss-Prot, P18302; M. musculus SH3P7: GenBank, U58884; D. discoideum coactosin: Swiss-Prot, P34121; S. cerevisiae Abp1: EMBL, X51780/Swiss-Prot, P15891; S. exiguus Abp1: Swiss-Prot, P38479; A. amurensis depactin: Swiss-Prot, P20690.
Figure 4
Figure 4
(a) Ribbon diagram of the yeast cofilin structure. Cofilin has a central mixed β-sheet, which is sandwiched between two pairs of α-helices. The positions of the insertions in mammalian cofilins are in green and blue, and the diverged region in twinfilins is in red. The highly conserved residues that appear to be important for protein stability and correct folding (Tyr64, Phe85, Trp88, Pro90, and Tyr101) are shown in yellow. (b) Space-filling model of yeast cofilin shown in two different orientations (rotated 180° around the y-axis). The residues that are essential for actin interactions in yeast cofilin are highlighted in red. The residues implicated in actin binding by peptide inhibition studies are in green. The highly conserved surface residues (Ser45, Met99, Ala102, Ser103, Gly114, and Gln120) are in orange. All of these residues, except Ser45, are located close to site of cofilin implicated genetically in actin binding, suggesting they also form part of the actin-binding surface. These Figures were produced using Midas Software (University of California San Francisco) running on a Silicon Graphics (Mountain View, CA) Indigo II workstation.
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