1re6: Difference between revisions

Revision as of 07:23, 3 May 2008

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

OverviewOverview

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.

About this StructureAbout this Structure

1RE6 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

Localization of dynein light chains 1 and 2 and their pro-apoptotic ligands., Day CL, Puthalakath H, Skea G, Strasser A, Barsukov I, Lian LY, Huang DC, Hinds MG, Biochem J. 2004 Feb 1;377(Pt 3):597-605. PMID:14561217 Page seeded by OCA on Sat May 3 07:23:18 2008

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OCA

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- {{Structure
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-|GENE= DLC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
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 '''Localisation of Dynein Light Chains 1 and 2 and their Pro-apoptotic Ligands'''
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 [[Category: Skea, G.]]
 [[Category: Strasser, A.]]
-[[Category: apoptosis]]
+[[Category: Apoptosis]]
-[[Category: dimer]]
+[[Category: Dimer]]
-[[Category: dynein light chain]]
+[[Category: Dynein light chain]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 07:23:18 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:27:02 2008''