5JOJ

Calcium-loaded EF-hand domain of L-plastin

5JOJ の概要

• エントリーDOI: 10.2210/pdb5joj/pdb
• 関連するPDBエントリー: 5JOL
• NMR情報: BMRB: 30071
• 分子名称: Plastin-2, CALCIUM ION (2 entities in total)
• 機能のキーワード: calcium-binding, ef-hand, l-plastin, metal binding protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm, cytoskeleton : P13796
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11048.61

構造登録者

Ishida, H.,Jensen, K.V.,Woodman, G.W.,Hyndman, M.E.,Vogel, H.J. (登録日: 2016-05-02, 公開日: 2017-04-19, 最終更新日: 2024-05-15)

主引用文献

Ishida, H.,Jensen, K.V.,Woodman, A.G.,Hyndman, M.E.,Vogel, H.J.
The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling.
Sci Rep, 7:40662-40662, 2017

PubMed Abstract: 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.

PubMed: 28145401
DOI: 10.1038/srep40662

実験手法

SOLUTION NMR