Related Experiment Video
Updated: Dec 12, 2025
07:40
Author Spotlight: Unveiling the Structural and Dynamic Aspects of Glycan Molecular Recognition
Published on: May 17, 2024
1.8K
Pro4 prolyl peptide bond isomerization in human galectin-7 modulates the monomer-dimer equilibrum to affect function
Michelle C Miller1, Irina V Nesmelova1, Vladimir A Daragan1
1Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455 U.S.A.
The Biochemical Journal
|August 9, 2020
Summary
Human galectin-7 (Gal-7) exists in two distinct conformations due to cis-trans isomerization, influencing its interactions and potentially acting as a molecular switch in cellular processes.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Human galectin-7 (Gal-7) is a multifunctional protein involved in various cellular processes.
- Gal-7 interacts with glycoconjugates and protein counter-receptors in different cellular compartments.
Purpose of the Study:
- To investigate the structural basis of Gal-7's multifunctionality.
- To explore the conformational dynamics of Gal-7 and their functional implications.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyze Gal-7 structure.
- Molecular dynamics simulations were employed to map hydrogen bonds and van der Waals interactions.
- Analysis of a P4L mutant was performed to confirm cis-trans isomerization.
Main Results:
- NMR revealed two distinct conformational states of Gal-7 in slow exchange, attributed to cis-trans isomerization at the P4 residue.
- Molecular dynamics simulations showed differences in N-terminal peptide mobility and solvent exposure between the cis and trans states.
- Both conformers exhibited similar binding affinity for lactose and cell surface contacts, but homodimer dissociation favored the cis-state at low concentrations.
Conclusions:
- Gal-7 isomerization represents a potential (patho)physiologically relevant molecular switch.
- These findings guide the mapping of Gal-7 binding sites for counter-receptors like Bcl-2, JNK1, p53, and Smad3.
- Further functional assays at low concentrations are recommended to validate the role of isomerization in Gal-7's biological functions.
More Related Videos
Related Concept Videos
01:05Proteoglycans
4.5K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
4.5K
01:29Protein Folding Quality Check in the RER
4.9K
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...
4.9K
02:43Peptide Bonds
81.2K
A peptide bond covalently attaches amino acids through a dehydration reaction. One amino acid's carboxyl group and another amino acid's amino group combine, releasing a water molecule. The resulting bond is the peptide bond. The products that such linkages form are peptides. As more amino acids join this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end has the N-terminal, or the amino-terminal, and the other end has a free...
81.2K
01:26Protein Modifications in the RER
6.5K
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...
6.5K
01:24Oligosaccharide Assembly
3.4K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
3.4K
00:49Ligand Binding and Linkage
5.3K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.3K