2q97
From Proteopedia
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Complex of mammalian actin with toxofilin from toxoplasma gondii
Overview
Many human pathogens exploit the actin cytoskeleton during infection, including Toxoplasma gondii, an apicomplexan parasite related to, Plasmodium, the agent of malaria. One of the most abundantly expressed, proteins of T. gondii is toxofilin, a monomeric actin-binding protein, (ABP) involved in invasion. Toxofilin is found in rhoptry and presents an, N-terminal signal sequence, consistent with its being secreted during, invasion. We report the structure of toxofilin amino acids 69-196 in, complex with the host mammalian actin. Toxofilin presents an extended, conformation and interacts with an antiparallel actin dimer, in which one, of the actins is related by crystal symmetry. Consistent with this, observation, analytical ultracentrifugation analysis shows that toxofilin, binds two actins in solution. Toxofilin folds into five consecutive, helices, which form three relatively independent actin-binding sites., Helices 1 and 2 bind the symmetry-related actin molecule and cover its, nucleotide-binding cleft. Helices 3-5 bind the other actin and constitute, the primary actin-binding region. Helix 3 interacts in the cleft between, subdomains 1 and 3, a common binding site for most ABPs. Helices 4 and 5, wrap around actin subdomain 4, and residue Gln-134 of helix 4 makes a, hydrogen-bonding contact with the nucleotide in actin, both of which are, unique features among ABPs. Toxofilin dramatically inhibits nucleotide, exchange on two actin molecules simultaneously. This effect is linked to, the formation of the antiparallel actin dimer because a construct lacking, helices 1 and 2 binds only one actin and inhibits nucleotide exchange less, potently.
About this Structure
2Q97 is a Protein complex structure of sequences from Oryctolagus cuniculus and Toxoplasma gondii with and as ligands. Full crystallographic information is available from OCA.
Reference
Toxofilin from Toxoplasma gondii forms a ternary complex with an antiparallel actin dimer., Lee SH, Hayes DB, Rebowski G, Tardieux I, Dominguez R, Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16122-7. Epub 2007 Oct 2. PMID:17911258
Page seeded by OCA on Wed Jan 23 12:06:22 2008
