Structural analysis of glyceraldehyde-3-phosphate dehydrogenase functional diversity

Multifunctional proteins provide a new mechanism to expand exponentially cell information and capability beyond that indicated by conventional gene analyses. As such, examination of their structure-function relationships provides a means to define the mechanisms through which cells accomplish critical yet disparate activities required for cell viability and survival. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) may be considered the quintessential multidimensional protein which exhibits a variety of functions unrelated to its classical role in energy production. This review discusses new insights into the structure-function mechanisms through which defined GAPDH amino acid domains are utilized for its diverse activities, the importance of its post-translational modification, and, intriguingly, the logic inherent in the presence or the absence of specific signaling domains.