Related Experiment Video
Updated: Jun 13, 2026
13:22
Adhesion Frequency Assay for In Situ Kinetics Analysis of Cross-Junctional Molecular Interactions at the Cell-Cell Interface
Published on: November 2, 2011
Two-state conformations in the hyaluronan-binding domain regulate CD44 adhesiveness under flow condition
Shinji Ogino1, Noritaka Nishida, Ryo Umemoto
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Structure (London, England : 1993)
|May 14, 2010
Summary
The CD44 receptor
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- CD44 is a receptor for hyaluronan (HA) crucial for leukocyte trafficking and tumor metastasis.
- Previous nuclear magnetic resonance (NMR) studies showed CD44's hyaluronan-binding domain (HABD) changes conformation upon HA binding.
Purpose of the Study:
- To investigate the conformational equilibrium of the HABD in the presence and absence of HA.
- To elucidate the role of HABD conformational states in CD44-mediated cell adhesion and rolling.
Main Methods:
- Nuclear magnetic resonance (NMR) spectroscopy to study HABD conformation.
- Analysis of HABD mutants with altered conformational preferences.
- Cell-based assays to measure CD44-mediated cell rolling efficiency.
Main Results:
- The HABD exists in an equilibrium between ordered (O) and partially disordered (PD) conformations, irrespective of HA presence.
- A mutant HABD favoring the PD conformation showed higher HA affinity but impaired cell rolling.
- Impaired rolling was attributed to decreased tether frequency and slower cellular off-rate.
Conclusions:
- The coexistence of high- and low-affinity states of the HABD is essential for efficient CD44-mediated cell rolling.
- This conformational flexibility is critical for leukocyte trafficking and potentially tumor metastasis.
More Related Videos
Related Concept Videos
01:25Structure of Cadherins
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
01:31Immunoglobulin-like Cell Adhesion Molecules
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:24Adherens Junctions
Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types – adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
The endothelial cells...
Adherens Junctions are Dynamic
The endothelial cells...
01:26Tension Response at Adherens Junctions
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...
00:49Ligand Binding and Linkage
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 the...