Mutational analysis of human profilin I reveals a second PI(4,5)-P2 binding site neighbouring the poly(L-proline) binding site.


BACKGROUND:Profilin is a small cytoskeletal protein which interacts with actin, proline-rich proteins and phosphatidylinositol 4,5-bisphosphate (PI(4,5)-P2). Crystallography, NMR and mutagenesis of vertebrate profilins have revealed the amino acid residues that are responsible for the interactions with actin and poly(L-proline) peptides. Although Arg88 of human profilin I was shown to be involved in PI(4,5)-P2-binding, it was suggested that carboxy terminal basic residues may be involved as well. RESULTS:Using site directed mutagenesis we have refined the PI(4,5)-P2 binding site of human profilin I. For each mutant we assessed the stability and studied the interactions with actin, a proline-rich peptide and PI(4,5)-P2 micelles. We identified at least two PI(4,5)-P2-binding regions in human profilin I. As expected, one region comprises Arg88 and overlaps with the actin binding site. The second region involves Arg136 in the carboxy terminal helix and neighbours the poly(L-proline) binding site. In addition, we show that adding a small protein tag to the carboxy terminus of profilin strongly reduces binding to poly(L-proline), suggesting local conformational changes of the carboxy terminal alpha-helix may have dramatic effects on ligand binding. CONCLUSIONS:The involvement of the two terminal alpha-helices of profilin in ligand binding imposes important structural constraints upon the functions of this region. Our data suggest a model in which the competitive interactions between PI(4,5)-P2 and actin and PI(4,5)-P2 and poly(L-proline) regulate profilin functions.


BMC Biochem


BMC biochemistry


Lambrechts A,Jonckheere V,Dewitte D,Vandekerckhove J,Ampe C





Has Abstract


2002-05-28 00:00:00








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    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Doucet C,Gutierrez GJ,Lindon C,Lorca T,Lledo G,Pinset C,Coux O

    更新日期:2005-12-01 00:00:00

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    journal_title:BMC biochemistry

    pub_type: 杂志文章


    authors: Edgar AJ

    更新日期:2002-06-25 00:00:00

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    pub_type: 杂志文章


    authors: Kalra S,Jena G,Tikoo K,Mukhopadhyay AK

    更新日期:2007-05-18 00:00:00

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    pub_type: 杂志文章,评审


    authors: Dahlmann B

    更新日期:2007-11-22 00:00:00