1RE6

Localisation of Dynein Light Chains 1 and 2 and their Pro-apoptotic Ligands

1RE6 の概要

• エントリーDOI: 10.2210/pdb1re6/pdb
• 分子名称: dynein light chain 2 (1 entity in total)
• 機能のキーワード: dynein light chain, apoptosis, dimer, contractile protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 21552.61

構造登録者

Day, C.L.,Puthalakath, H.,Skea, G.,Strasser, A.,Barsukov, I.,Lian, L.Y.,Huang, D.C.,Hinds, M.G. (登録日: 2003-11-06, 公開日: 2004-03-23, 最終更新日: 2024-05-22)

主引用文献

Day, C.L.,Puthalakath, H.,Skea, G.,Strasser, A.,Barsukov, I.,Lian, L.Y.,Huang, D.C.,Hinds, M.G.
Localization of dynein light chains 1 and 2 and their pro-apoptotic ligands.
Biochem.J., 377:597-605, 2004

PubMed Abstract: The dynein and myosin V motor complexes are multi-protein structures that function to transport molecules and organelles within the cell. DLC (dynein light-chain) proteins, found as components of both dynein and myosin V motor complexes, connect the complexes to their cargoes. One of the roles of these motor complexes is to selectively sequester the pro-apoptotic 'BH3-only' (Bcl-2 homology 3-only) proteins, Bim (Bcl-2-interacting mediator of cell death) and Bmf (Bcl-2-modifying factor), and so regulate their cell death-inducing function. In vivo DLC2 is found exclusively as a component of the myosin V motor complex and Bmf binds DLC2 selectively. On the other hand, Bim interacts with DLC1 (LC8), an integral component of the dynein motor complex. The two DLCs share 93% sequence identity yet show unambiguous in vivo specificity for their respective BH3-only ligands. To investigate this specificity the three-dimensional solution structure of DLC2 was elucidated using NMR spectroscopy. In vitro structural and mutagenesis studies show that Bmf and Bim have identical binding characteristics to recombinant DLC2 or DLC1. Thus the selectivity shown by Bmf and Bim for binding DLC1 or DLC2, respectively, does not reside in their DLC-binding domains. Remarkably, mutational analysis of DLC1 and DLC2 indicates that a single surface residue (residue 41) determines the specific localization of DLCs with their respective motor complexes. These results suggest a molecular mechanism for the specific compartmentalization of DLCs and their pro-apoptotic cargoes and implicate other protein(s) in defining the specificity between the cargoes and the DLC proteins.

PubMed: 14561217

実験手法

SOLUTION NMR