[Frontiers in Bioscience 14, 3246-3258, January 1, 2009]
Sensing NAD metabolites through macro domains
Susanne Till, Andreas G. Ladurner
European Molecular Biology Laboratory (EMBL), Gene Expression Unit, Structural and Computational Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany
TABLE OF CONTENTS
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.