Crystal structure of the actin-binding protein actophorin from Acanthamoeba

Leonard, Shonda A.; Gittis, Apostolos G.; Petrella, Eugene C.; Pollard, Thomas D.; Lattman, Eaton E.

doi:10.1038/nsb0597-369

Cited by 73 publications

(69 citation statements)

References 27 publications

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“…that the ␣-helix was interrupted (Fedorov et al 1997;Leonard et al 1997). We recently confirmed the presence of a similar distortion in porcine destrin (Hatanaka & Moriyama, unpublished results).…”

Section: Temperature-sensitive Mutations Of Cofilinsupporting

confidence: 64%

Cooperation of two actin‐binding proteins, cofilin and Aip1, in Saccharomyces cerevisiae

Iida

Yahara

1999

Genes to Cells

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Background: Cofilin is a low-molecular weight actinmodulating protein, and is structurally and functionally conserved among eukaryotes. Cofilin is encoded by COF1 in Saccharomyces cerevisiae, and is essential for cell viability. Cofilin binds to and severs actin filaments in vitro, and also enhances their depolymerization. A partner protein that cooperates with cofilin in vivo has not been identified.

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Section: Temperature-sensitive Mutations Of Cofilinsupporting

confidence: 64%

Cooperation of two actin‐binding proteins, cofilin and Aip1, in Saccharomyces cerevisiae

Iida

Yahara

1999

Genes to Cells

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“…34). An Ala to Gly mutation at position 118 should have little impact on the overall structure of the helix, although it might enhance the flexibility of the type I ␤-turn, which has been reported to distort the long ␣-helix in the actophorin structure (34). Distortions of this helix have also been reported for destrin and yeast cofilin (32,33) and models for the cofilin binding sight on F-actin emphasize the possible significance of this distortion (49).…”

mentioning

confidence: 96%

“…These actin and PIP 2 binding regions are highly conserved in the equivalent plant ADF sequences (9). The tertiary structures of destrin, yeast cofilin, and Acanthamoeba actophorin have recently been reported from nuclear magnetic resonance studies (32) and x-ray analysis (33,34). All three structures have the same basic fold and show that the two sequences, Trp-104 to Met-115 and Asp-122 to Leu-128 in destrin are located at the N and C termini, respectively, of the long ␣-helix starting at Leu-111 and terminating at Phe-128.…”

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confidence: 99%

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F-actin and G-actin binding are uncoupled by mutation of conserved tyrosine residues in maize actin depolymerizing factor (ZmADF)

Jiang

Weeds

Khan

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Actin depolymerizing factors (ADF) are stimulus responsive actin cytoskeleton modulating proteins. They bind both monomeric actin (G-actin) and filamentous actin (F-actin) and, under certain conditions, F-actin binding is followed by filament severing. In this paper, using mutant maize ADF3 proteins, we demonstrate that the maize ADF3 binding of F-actin can be spatially distinguished from that of G-actin. One mutant, zmadf3-1, in which Tyr-103 and Ala-104 (equivalent to destrin Tyr-117 and Ala-118) have been replaced by phenylalanine and glycine, respectively, binds more weakly to both G-actin and F-actin compared with maize ADF3. A second mutant, zmadf3-2, in which both Tyr-67 and Tyr-70 are replaced by phenylalanine, shows an affinity for G-actin similar to maize ADF3, but F-actin binding is abolished. The two tyrosines, Tyr-67 and Tyr-70, are in the equivalent position to Tyr-82 and Tyr-85 of destrin, respectively. Using the tertiary structure of destrin, yeast cofilin, and Acanthamoeba actophorin, we discuss the implications of removing the aromatic hydroxyls of Tyr-82 and Tyr-85 (i.e., the effect of substituting phenylalanine for tyrosine) and conclude that Tyr-82 plays a critical role in stabilizing the tertiary structure that is essential for F-actin binding. We propose that this tertiary structure is maintained as a result of a hydrogen bond between the hydroxyl of Tyr-82 and the carbonyl of Tyr-117, which is located in the long ␣-helix; amino acid components of this helix (Leu-111 to Phe-128) have been implicated in G-actin and F-actin binding. The structures of human destrin and yeast cofilin indicate a hydrogen distance of 2.61 and 2.77 Å, respectively, with corresponding bond angles of 99.5°and 113°, close to the optimum for a strong hydrogen bond.

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“…The so called "headpiece" of villin also competes with ADF for binding to actin (61), but only partial and weak competition was evident between ␣-actinin and cofilin (60). The structures of three cofilins, ADF (29), yeast cofilin (69), and actophorin (70), have been determined. Interestingly, cofilins have an overall fold similar to the gelsolin segment 1 (G1) (27), leading some others (29,63) to suggest that ADF-cofilin binds actin in a similar manner as G1.…”

Section: Involvement Of Actin Subdomain 1 In the Interaction Withmentioning

confidence: 99%

The Identification of a Second Cofilin Binding Site on Actin Suggests a Novel, Intercalated Arrangement of F-actin Binding

Renoult

Ternent²,

Maciver³

et al. 1999

Journal of Biological Chemistry

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The cofilins are members of a protein family that binds monomeric and filamentous actin, severs actin filaments, and increases monomer off-rate from the pointed end. Here, we characterize the cofilin-actin interface. We confirm earlier work suggesting the importance of the lower region of subdomain 1 encompassing the N and C termini (site 1) in cofilin binding. In addition, we report the discovery of a new cofilin binding site (site 2) from residues 112-125 that form a helix toward the upper, rear surface of subdomain 1 in the standard actin orientation (Kabsch, W., Mannherz, H. G., Suck, D., Pai, E. F., and Holmes, K. C. (1990) Nature 347, 37-44). We propose that cofilin binds "behind" one monomer and "in front" of the other longitudinally associated monomer, accounting for the fact that cofilin alters the twist in the actin (McGough, A., Pope, B., Chiu, W., and Weeds, A. (1997) J. Cell Biol. 138, 771-781). The characterization of the cofilin-actin interface will facilitate an understanding of how cofilin severs and depolymerizes filaments and may shed light on the mechanism of the gelsolin family because they share a similar fold with the cofilins (Hatanaka, H., Ogura, K., Moriyama, K., Ichikawa, S., Yahara, I., and Inagiki, F. (1996) Cell 85, 1047-1055).Many motile processes in cells require cyclic polymerization and depolymerization of actin filaments. In cell locomotion for example, actin is polymerized at the leading edge of the cell and is recycled by depolymerizing toward the cell center. The rate constants of pure actin have been established (1), and it is clear that a discrepancy exists between these known rates and those calculated from filament turnover in cells (2). A host of actinbinding proteins are known that dramatically alter the behavior of actin in vitro, and of these, the cofilins have been suggested to have the correct properties to increase filament turnover in cells (3). This view has been confirmed by studies with living Saccharomyces (4) and Dictyostelium (5) and by Listeria motility assays (6, 7).The cofilins are a group of low molecular mass (15-21 kDa), actin-binding proteins that depolymerize actin filaments (8).This group includes vertebrate cofilin (9) and ADF 1 (10), twinstar from Drosophila (11), depactin from echinoderms (12), ADFs from plants (13), Unc-60 from nematode (14), cofilins from Saccharomyces (15, 16) and Dictyostelium (17), and actophorin from Acanthamoeba castellanii (18).The mechanism by which cofilin depolymerizes actin filament has been contentious. Soon after the discovery of the first member of the family (10), several authors suggested that depolymerization occurred through severing (9, 18). Evidence for a severing mechanism later came from videomicroscopy (19,20), but this was later challenged (6) as it was shown (6, 21) that cofilins increased the off-rate from the pointed end of the filament. However, the two opinions are not necessarily exclusive (22-24), and a similar mechanism has been proposed for both events (23). We report the identification of a cof...

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Crystal structure of the actin-binding protein actophorin from Acanthamoeba

Abstract: Actophorin is a member of the actin-depolymerizing factor/cofilin family. It severs actin filaments and sequesters actin monomers. The crystal structure of actophorin will help to elucidate actin-ADF/cofilin interactions.

Cited by 73 publications

References 27 publications

Cooperation of two actin‐binding proteins, cofilin and Aip1, in Saccharomyces cerevisiae

Cooperation of two actin‐binding proteins, cofilin and Aip1, in Saccharomyces cerevisiae

F-actin and G-actin binding are uncoupled by mutation of conserved tyrosine residues in maize actin depolymerizing factor (ZmADF)

The Identification of a Second Cofilin Binding Site on Actin Suggests a Novel, Intercalated Arrangement of F-actin Binding

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