Structural highlights
Function
PLSL_HUMAN Actin-binding protein. Plays a role in the activation of T-cells in response to costimulation through TCR/CD3 and CD2 or CD28. Modulates the cell surface expression of IL2RA/CD25 and CD69.[1] [2]
Publication Abstract from PubMed
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.
The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling.,Ishida H, Jensen KV, Woodman AG, Hyndman ME, Vogel HJ Sci Rep. 2017 Feb 1;7:40662. doi: 10.1038/srep40662. PMID:28145401[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Janji B, Giganti A, De Corte V, Catillon M, Bruyneel E, Lentz D, Plastino J, Gettemans J, Friederich E. Phosphorylation on Ser5 increases the F-actin-binding activity of L-plastin and promotes its targeting to sites of actin assembly in cells. J Cell Sci. 2006 May 1;119(Pt 9):1947-60. PMID:16636079 doi:http://dx.doi.org/10.1242/jcs.02874
- ↑ Wabnitz GH, Kocher T, Lohneis P, Stober C, Konstandin MH, Funk B, Sester U, Wilm M, Klemke M, Samstag Y. Costimulation induced phosphorylation of L-plastin facilitates surface transport of the T cell activation molecules CD69 and CD25. Eur J Immunol. 2007 Mar;37(3):649-62. PMID:17294403 doi:http://dx.doi.org/10.1002/eji.200636320
- ↑ Ishida H, Jensen KV, Woodman AG, Hyndman ME, Vogel HJ. The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling. Sci Rep. 2017 Feb 1;7:40662. doi: 10.1038/srep40662. PMID:28145401 doi:http://dx.doi.org/10.1038/srep40662
