The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling

L-plastin is a calcium-regulated actin-bundling protein that is expressed in cells of hematopoietic origin and in most metastatic cancer cells. These cell types are mobile and require the constant remodeling of their actin cytoskeleton, where L-plastin bundles filamentous actin. The calcium-dependent regulation of the actin-bundling activity of L-plastin is not well understood. We have used NMR spectroscopy to determine the solution structure of the EF-hand calcium-sensor headpiece domain. Unexpectedly, this domain does not bind directly to the four CH-domains of L-plastin. A novel switch helix is present immediately after the calcium-binding region and it binds tightly to the EF-hand motifs in the presence of calcium. We demonstrate that this switch helix plays a major role during actin-bundling. Moreover a peptide that competitively inhibits the association between the EF-hand motifs and the switch helix was shown to deregulate the actin-bundling activity of L-plastin. Overall, these findings may help to develop new drugs that target the L-plastin headpiece and interfere in the metastatic activity of cancer cells.

• Publication year

  2017

• Venue

  Scientific Reports

• Publication date

  2017-02-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/srep40662PMID 28145401PMCID 5286426
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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