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Latrunculin

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An actin-binding toxin produced by various species of sponge (e.g. Negombata magnifica) from the Red Sea.  Latrunculin inhibits actin polymerisation in vitro (Coue et al, 1987; Morton et al, 2000) and in vivo (Spector et al, 1983).  The structure of latrunculin A free and bound to actin has been solved crystallographically (Morton et al, 2000), confirming suspicions that the binding site was close to the nucleotide binding site (Ayscough, K.R. et al, 1997; Belmont et al, 1999). The lantrunculin binding site is between subdomains 2 and 4, tyrosine 69 in subdomain 2, threonine 186 and arginine 210 in subdomain 4 form hydrogen bounds with the drug in good agreement with the previous studies in which the latrunculin binding site was tested by mutagenesis and screening for the retention of drug binding (Belmont et al, 1999).   Latrunculin binds actin independently to profilin and DNase1, but competes with thymosin b4 (Yarmola et al, 2000). 
Latrunculin A
Latrunculin A binds G-actin with modrate affinity (0.2um) (Coue et al, 1987; Yarmola et al, 2000), and it inhibits the rate of nucleotide exchange (Ayscough et al, 1997; Yarmola et al, 2000) in line with its binding site between sub-domains 1 and 4.  Binding latrunculin A causes alterations in the structure of G-actin that preclude its participation in polymerization (Morton et al, 2000)

 

References:-

Ayscough, K.R., Stryker, J., Pokala, N., Sanders, M., Crews, P. & Drubin, D.G. (1997). "" J.Cell Biol. 137, 399-416.

Bar-Ziv, R., T. , Tlusty, T., Moses, E., Safran, S.A. & Bershadsky, A.

Belmont, L.D., Patterson, G.M.L., & Drubin, D.G. (1999). "New actin mutants allow further characterization of the nucleotide binding cleft and drug binding sites." J.Cell Sci. 112, 1325-1336.

Coue, M., Brenner, S.L., Spector, I., & Korn E.D., ( 1987). "Inhibition of actin polymerization by latrunculin A". FEBS letters. 213, 316-318.

Gronewold, T.M.A., Sasse, F., Lündsdorf, H. & Reichenbach, H. (1999). "Effects of rhizopodin and latrunculin B on the morphology and on the actin cytoskeleton of mammalian cells." Cell Tissue Research 295, 121-129.

Morton, W. M., Ayscough, K.R., & McLaughlin, P.J. (2000). "Latrunculin alters the actin-monomer subunit interface to prevent polymerization." Nature Cell Biol. 2, 376-378.

Pendleton, A. &  Koffer, A. (2001). "Effects of latrunculin reveal requirements for the actin cytoskeleton during secretion from mast cells". Cell Motility Cytoskeleton. 48,  37-51.

Spector, I., Shochet, N.R., Kashman, Y. & Groweiss, A. (1983). Science 214, 493-495.

Yarmola, E.G., Somasundaram, T., Boring, T.A., Spector, I. & Bubb, M.R. (2000). "Actin-latrunculin A structure and function." J.Biol.Chem. 275(36), 28120-28127.

 
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