Kaela Bernecky/Sandbox1.
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Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
Function in animal cells
GAPDH is a ubiquitous protein found in all organisms that undergo glyclolysis.There is only one isoform of GAPDH in animal cells, in animal cells GAPDH is used to convert glyceraldehyde-3-phosphate dehyrogenase into 1,3-bisphosphoglyerate with a cofacter NAD getting converted to NADH.
Funtion in Plant cells
In plant cells there are four gapA,gapB, gapC, and gapCp. [1] Of the isoforms in plants gapA and gapB produce the enzymes GAPA and GAPB used in the Calvin cycle [1]. The Calvin-Benson-Basham cycle, it converts 1,3 bisphosphoglycerate to glyceraldehyde-3-phosphate [2]. This enzyme is found in the chloroplasts of plants and forms a complex with phosphoribulokinase (PKR) and a small chloroplast protein (CP12). This complex keeps the Calvin cycle light dependent [3]
Regulatory proteins
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[3]. CP12 is a linker protein that forms a complex with GAPDH and PRK and is regulated by oxidation [4]In the dimer form, GAPDH is regulated by C-terminal extension of the B subunits. [5] These C-terminal extensions work like hooks to block the binding sites in the B subunits, but leave the A subunits open.[5]. GAPDH can be inhibited by the oxidation of cysteines found in the C-terminal [5]. The binding site for NAD has been experimentally predicted at Cys200 of GAPA using a mutation for alanine [6].
Signaling
GAPDPH is used for cell signaling in both plants and animal cells. In plant cells salicylic acid can bind to the GAPA subunit [7]. Salicylic acid initiates metabolic changes in plants depending on what it binds to [7]. This binding site is believe to be the same site as the NAD cofactor in glycolysis [7].
Relevance
GAPDH is a protein found in most living organisms that undergo glycolysis or the Calvin cycle. GAPDH research in plants focuses on crop growth and yield, while in animals, GAPDH research is focused on disease. GAPDH is involved with immune response and cell death [8] GAPDH is used in autoimmune research, because it is associated with inflammation and it is a rate limiting enzyme when glycolysis is increased [8].
Recent plant research being conducted, focuses on increasing crop growth by altering the GAPDH proteins.[2]Mutations of GAPDH B subunit can cause decreased levels of photosynthesis in plants. [3].
A recent study using a plant sesterterpenoid irreversibly binding to GAPDH found that GAPDH levels would diminish, which would be beneficial for an autoimmune treatment [8].
Structural highlights
GAPDH from plants can have a quaternary structure composed of two dimers or a homotetramer of A chains.[5] GAPA and GAPB [2]. GAPB has the chains FA and F while GAPA has the chains EA and E. The GAPA subunits contain binding the binding sites for NAD and salicylic acid, while the GAPB subutis work to regulate the GAPA binding sites[1].
- ↑ 1.0 1.1 1.2 Zaffagnini M, Fermani S, Costa A, Lemaire SD, Trost P. Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting properties. Front Plant Sci. 2013 Nov 12;4:450. doi: 10.3389/fpls.2013.00450. PMID: 24282406; PMCID: PMC3824636.
- ↑ 2.0 2.1 2.2 Glyceraldehyde-3-phosphate dehydrogenase subunits A and B are essential to maintain photosynthetic efficiency. Plant Physiol. 2023 Aug 3;192(4):2989-3000. doi: 10.1093/plphys/kiad256. PMID: 37099455; PMCID: PMC11025378
- ↑ 3.0 3.1 3.2 Inter-species variation in the oligomeric states of the higher plant Calvin cycle enzymes glyceraldehyde-3-phosphate dehydrogenase and phosphoribulokinase. J Exp Bot. 2011 Jul;62(11):3799-805. doi: 10.1093/jxb/err057. Epub 2011 Apr 15. PMID: 21498632; PMCID: PMC3134340.
- ↑ Delobel A, Graciet E, Andreescu S, Gontero B, Halgand F, Laprévote O. Mass spectrometric analysis of the interactions between CP12, a chloroplast protein, and metal ions: a possible regulatory role within a PRK/GAPDH/CP12 complex. Rapid Commun Mass Spectrom. 2005;19(22):3379-88. doi: 10.1002/rcm.2192. PMID: 16259044.
- ↑ 5.0 5.1 5.2 5.3 Marotta R, Del Giudice A, Gurrieri L, Fanti S, Swuec P, Galantini L, Falini G, Trost P, Fermani S, Sparla F. Unravelling the regulation pathway of photosynthetic AB-GAPDH. Acta Crystallogr D Struct Biol. 2022 Nov 1;78(Pt 11):1399-1411. doi: 10.1107/S2059798322010014. Epub 2022 Oct 27. PMID: 36322422
- ↑ Fermani S, Sparla F, Marri L, Thumiger A, Pupillo P, Falini G, Trost P. Structure of photosynthetic glyceraldehyde-3-phosphate dehydrogenase (isoform A4) from Arabidopsis thaliana in complex with NAD. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Jun 1;66(Pt 6):621-6. doi: 10.1107/S1744309110013527. Epub 2010 May 25. PMID: 20516587; PMCID: PMC2882757.
- ↑ 7.0 7.1 7.2 Pokotylo I, Hellal D, Bouceba T, Hernandez-Martinez M, Kravets V, Leitao L, Espinasse C, Kleiner I, Ruelland E. Deciphering the Binding of Salicylic Acid to Arabidopsis thaliana Chloroplastic GAPDH-A1. Int J Mol Sci. 2020 Jun 30;21(13):4678. doi: 10.3390/ijms21134678. Erratum in: Int J Mol Sci. 2020 Oct 09;21(20):E7435. doi: 10.3390/ijms21207435. PMID: 32630078; PMCID: PMC7370300.
- ↑ 8.0 8.1 8.2 Zhou TT, Zheng Y, Zhang MW, Gong LH, Guo K, He XP, Liu YC, Gershenzon J, Liu Y, Li SH. Plant defense-directed discovery of a natural anti-psoriasis agent targeting GAPDH. Sci Adv. 2025 Jul 25;11(30):eadw2578. doi: 10.1126/sciadv.adw2578. Epub 2025 Jul 25. PMID: 40712011; PMCID: PMC12292834.
