Sensing NAD metabolites through macro domains.
The macro module is a globular protein domain of about 25 kDa that is evolutionarily conserved in organisms from viruses, bacteria, yeast to humans. It is generally part of proteins that have wide-ranging (and yet to be discovered) cellular functions. There are several examples of macro domains associated with modules showing homology to poly-ADP-ribosyl-polymerases. Many macro domains, including those of the human histone macroH2A1.1, bind NAD metabolites such as ADP-ribose, suggesting that macro domains may function in the recognition of this and related molecules. The presence of a metabolite-binding function in a repressive chromatin component opens new potential connections between chromosome structure, gene silencing and cellular metabolism. Current evidence suggests that macro domains also represent a novel tool for studying NAD metabolites and may be an attractive drug target for the treatment of diseases.
Till
Susanne
S
European Molecular Biology Laboratory (EMBL), Gene Expression Unit, Structural and Computational Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Ladurner
Andreas G
AG
D001419:Bacteria / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014780:Viruses / Q000378:metabolism
D006657:Histones; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases