Moonlighting Function of the Tubulin Cytoskeleton: Macromolecular Architectures in the Cytoplasm - Systems Biology of Metabolic and Signaling Networks - page 163

Fig. 7.1 PFK and MT: ultrastructure-dependent functions. (a): Periodical cross-linking of MTs by
tetrameric PFK formed by dimer-dimer association of PFK bound primarily to MTs. (b): the
addition of aldolase to the partial dissociated PFK prevents further dilution-induced dissociation,
thus the inactivation of PFK. (c): Schematic presentation of multiple interactions in

MT-PFK-aldolase system

a very small fraction of the genome ( http://www.ornl.gov/sci/techresources/
Human_Genome/faq/genenumber.shtml ) .
The molecular functions of many of the products of these genes have yet to be
assigned; in addition, the network of all macromolecular interactions at gene and
protein levels is far from being worked out. It requires the integration of many
different kinds of experimental and computational methods. A functional genomic
strategy using metabolome data revealed the phenotypes conferred by silent
mutations (M/2) and the complex mechanisms leading from a single gene mutation
to a highly variable phenotype (Raamsdonk et al. 2001 ).
The existence of moonlighting proteins is generally acknowledged. Their multi-
ple functions do not result from gene fusions, splice variants, or posttranslational
modifications (Jeffery 2003 ) but rather from the same protein having different
functions depending on its location in a particular compartment, on its oligomeri-
zation state, or on its interaction with other molecular partners (Fig. 7.2 ). These
features are not coded in the genome sequences, thus making the prediction of the
moonlighting characteristics of gene products almost impossible. This has not
precluded data on moonlighting proteins accumulating and being categorized
(Sriram et al. 2005 ).
An excellent example of a classic metabolic enzyme displaying moonlighting
characteristics is glyceraldehyde-3-phosphate dehydrogenase (GAPDH). This gly-
colytic enzyme has distinct functions that depend on its oligomerization state and
location within the cell: the tetramer catalyzes the conversion of 3-
phosphoglyceraldehyde in the cytosol, whereas the monomer catalyzes the release
of uracil from DNA in the nucleus (Meyer-Siegler et al. 1991 ). The oligomerization
state of this enzyme is modulated by the cellular concentrations of adenosine
triphosphate (ATP) and nicotinamide-adenine-dinucleotide (NAD + ), and by its
interactions with potential partners such as function-related glycolytic enzymes
(Olah et al. 2008 ). The truncated toxic polypeptide derived from the β -amyloid