Related Experiment Video
Updated: May 2, 2026
11:25
Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
Published on: October 4, 2017
6.0K
Transglutaminase 2 undergoes a large conformational change upon activation
Daniel M Pinkas1, Pavel Strop, Axel T Brunger
1Department of Chemical Engineering, Stanford University, Stanford, California, United States of America.
Plos Biology
|December 21, 2007
Summary
Researchers visualized human transglutaminase 2 (TG2) in an active state, revealing its catalytic tunnel. This breakthrough aids understanding of TG2
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Human transglutaminase 2 (TG2) is crucial in extracellular matrix biology and implicated in celiac disease pathogenesis.
- Previous studies crystallized TG2 in inactive conformations with inaccessible active sites.
Purpose of the Study:
- To determine the structure of human TG2 in an active conformation.
- To elucidate the mechanism of TG2 catalysis and its role in celiac disease.
Main Methods:
- X-ray crystallography at 2-Å resolution of human TG2 complexed with an inhibitor.
- Site-directed mutagenesis to investigate the enzyme's active site.
Main Results:
- The crystal structure revealed TG2 in an extended conformation with an exposed active site.
- Catalysis occurs within a tunnel bridged by tryptophan residues, stabilizing reaction intermediates.
- Mutants showed increased hydrolysis preference over transamidation.
Conclusions:
- The study provides the first visualization of an activated TG2 conformer, offering insights into its catalytic mechanism.
- Understanding TG2's structure and function is vital for dissecting its roles in biology and the autoimmune response in celiac sprue.
More Related Videos
Related Concept Videos
01:26Protein Modifications in the RER
5.6K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.6K
01:29Protein Folding Quality Check in the RER
4.4K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
4.4K
01:27Post-translational Translocation of Proteins to the RER
5.6K
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
5.6K
01:16TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
01:22Activation and Inactivation of G Proteins
8.9K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
8.9K
01:22Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
1.3K
Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
1.3K