Multiple Binding Partners

Abstract

GAPDH interacts with a plethora of diverse cellular proteins. The network of interacting partners, or interactome, is presented for GAPDH with the interacting molecules grouped into specific functional and structural categories. By organizing the binding partners in this way, certain common structural features are beginning to surface, such as acidic dipeptide sequences that are found in several of these binding proteins. Additionally, the consensus sequences for target polynucleotides are being brought to light. The categories, which are presented according to function, offer an opportunity for research into the corresponding structural correlates to these interactions. Recent discoveries of interacting proteins have revealed novel relationships that are generating emerging mechanisms. Proteins that are associated with age-related neurodegenerative diseases appear to be particularly prone to binding GAPDH, suggesting that GAPDH may be playing a role in these diseases. Neurodegenerative diseases that are discussed are the conformational diseases of aging, suggesting that GAPDH may be a global sensor for cellular conformational stress. In addition to GAPDH's oxidoreductase activity, several other enzymatic functions have been discovered, including peroxidase, nitrosylase, mono-ADP-ribosylase and kinase activities.

N-acetyl ornithine deacetylase is a moonlighting protein and is involved in the adaptation of Entamoeba histolytica to nitrosative stress

“…GAPDH interacts with numerous proteins of diverse functions (for a review see ref. 58). To the best our knowledge, this is the first report which describes an interaction between GAPDH and NAOD.…”

Glyceraldehyde 3‐phosphate dehydrogenase augments the intercellular transmission and toxicity of polyglutamine aggregates in a cell model of Huntington disease

“…The interactome of GAPDH includes proteins with a role in the membrane transport of proteins, G‐proteins, Ca 2+ ‐binding protein extracellular binding targets, molecular chaperones, and others. The target proteins relevant to our study include misfolded proteins like amyloid β peptide, tau, α‐synuclein and HTT (Seindler ). Recently, we showed that not only is GAPDH present in polyQ aggregates, but it can also augment the latter aggregation (Guzhova et al .…”

Isoflurane Enhances the Moonlighting Activity of GAPDH: Implications for GABAA Receptor Trafficking

“…There is an increased recognition of GAPDH's multifunctionality, particularly with regard to neuronal function [2]. We think that in addition to this role (i.e., kinase-dependent phosphorylation of the receptor [1]), GAPDH may also participate in the proper receptor trafficking to the plasma membrane, and perhaps the recycling event.…”