2N5R

NMR structure of cFLIP-derived calmodulin binding peptide

2N5R の概要

• エントリーDOI: 10.2210/pdb2n5r/pdb
• NMR情報: BMRB: 25726
• 分子名称: CASP8 and FADD-like apoptosis regulator (1 entity in total)
• 機能のキーワード: calmodulin, apoptosis
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1561.98

構造登録者

Panaitiu, A.E. (登録日: 2015-07-24, 公開日: 2015-11-18, 最終更新日: 2024-05-15)

主引用文献

Gaidos, G.,Panaitiu, A.E.,Guo, B.,Pellegrini, M.,Mierke, D.F.
Identification and Characterization of the Interaction Site between cFLIPL and Calmodulin.
Plos One, 10:e0141692-e0141692, 2015

PubMed Abstract: Overexpression of the cellular FLICE-like inhibitory protein (cFLIP) has been reported in a number of tumor types. As an inactive procaspase-8 homologue, cFLIP is recruited to the intracellular assembly known as the Death Inducing Signaling Complex (DISC) where it inhibits apoptosis, leading to cancer cell proliferation. Here we characterize the molecular details of the interaction between cFLIPL and calmodulin, a ubiquitous calcium sensing protein. By expressing the individual domains of cFLIPL, we demonstrate that the interaction with calmodulin is mediated by the N-terminal death effector domain (DED1) of cFLIPL. Additionally, we mapped the interaction to a specific region of the C-terminus of DED1, referred to as DED1 R4. By designing DED1/DED2 chimeric constructs in which the homologous R4 regions of the two domains were swapped, calmodulin binding properties were transferred to DED2 and removed from DED1. Furthermore, we show that the isolated DED1 R4 peptide binds to calmodulin and solve the structure of the peptide-protein complex using NMR and computational refinement. Finally, we demonstrate an interaction between cFLIPL and calmodulin in cancer cell lysates. In summary, our data implicate calmodulin as a potential player in DISC-mediated apoptosis and provide evidence for a specific interaction with the DED1 of cFLIPL.

PubMed: 26529318
DOI: 10.1371/journal.pone.0141692

実験手法

SOLUTION NMR