Adhesion molecules

These cell surface glycoproteins can be divided into four main groups :

  1. The integrin family (8 subfamilies; for example beta 1 : CD29, VLA=Very Late Activator ; beta 2 : leukocyte integrins such as CD11/CD18)
  2. The immunoglobulin superfamily (for example LFA-2=CD2 , LFA-3=CD58 , ICAMs=intercellular adhesion molecules , VCAM-1=vascular adhesion molecule-1)
  3. Selectins (P, E, L) ; they contain lectin domain
  4. Cadherins (E=epithelial, P=placental, N=neural subclasses)

The binding sites are different for each of these adhesion molecules. They are essential for contacts between the cells and between the cells and extracellular matrix (ECM).

Integrins are cell-surface receptors that mediate adhesion to the extracellular matrix (ECM) and cell-cell interactions. Most cells express several integrins that recognize a range of cell surface- and ECM- associated ligands. Individual integrins often bind more than one ligand. They play multiple roles in differentiation and cell communication.
Integrins are heterodimers of alpha and beta subunits :

Many integrins recognize the sequence RGD (Arg-Gly-Asp).
In mammals, at least 20 integrin heterodimers, comprised of 14 different types of alpha subunits and 8 types of beta subunits are known ( 5 ). A single beta chain can interact with multiple alpha chains forming integrins that bind different ligands. Some of the subunits are expressed exclusively on one type of cells, for example:

Some integrins may require activation in order to bind their ligand and anchor the cell to the ECM or to another cell. For example alphaIIb beta3 integrin (Ca(2+) dependent heterodimer) from platelets cannot bind fibrinogen (blood fibrous protein) unless the platelets are are activated by binding collagen or thrombin in a forming clot. This activation leads to conformational change in the integrin which is connected with cytoskeleton remodeling. Adhesion mediated by alphaIIb beta3 integrin is selective and irreversible. It plays a central role in thrombus formation in health and disease (the simultaneous occupation of receptors on adjacent platelets with dimeric fibronectin molecules leads to platelet aggregation). Besides fibrinogen it also binds von Willebrant Factor (vWF), fibronectin, vitronectin and thrombospondin.( 3 )

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The Ig superfamily members contain I-domains. X-ray crystallography revealed that I-domain consists of central core of 5 parallel and one short antiparallel beta-strands surrounded at the outer surface by 7 alpha-helices and loop regions. It contains about 200 amino acid residues. Each I-domain has the disulphide bridge. ( 6 )

One of the member of the Ig superfamily is CD2, a glycoprotein receptor of T-cells. It mediates cell-cell adhesion by binding to the surface molecule LFA-3 (from the same group) present on many cells including APC (antigen presenting cells). CD2 has two extracellular I-domains. N-terminal domain which is responsible for adhesion contains a single high-mannose type oligosaccharide. The absence of this N-glycan leads to loss of both structural and functional properties of CD2 ( 6 )

CD2 - LFA 3 adhesion plays an important role in faciliating TCR/CD3 recognition of antigens presented by the MHC class II. CD2 is also required for T-cell activation.

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Selectins are membrane-attached mosaic proteins recognizing carbohydrates.

They consist of small cytosolic domain , single transmembrane helix, EGF-domain and N-terminal lectin (CRD= carbohydrate recognition domain ; it belongs to C-type animal lectins , which are Ca (2+)- dependent)

Due to the selectins white blood cells can migrate from blood vessels to the tissues. They adhere selectively to the walls of blood vessels called high endothelial venules (microscopic vessels, less than 30 microns in diameter). This adhesion is mediated by the L-selectins (homing receptors) on lymphocytes. They determine the endothelial cells to which a lymphocytes will adhere (for example some of them bind only in peripheral lymph nodes the others in the intestinal Peyer's patches)

In contrast to the homing receptor, the two other selectins (P and E) are found on endothelial cells and then only when they are actively attracting leukocytes (they are transiently expressed on endothelial cells).

When a tissue is infected, it secretes cytokines (IL-1, TNF) which stimulate endothelial cells in the venules to express P and E selectins. The white blood cells adhere to these selectins because their carohydrate coats contain complementary structures. Thus leukocytes can leave the vessels and migrate into the infected tissue.

P and E selectins appear on endothelial cells at different times and recruit different types of ehite blood cells.

In some diseases white blood cells enter the tissues where they not belong and cause their damage. For example the inflammation of rheumatoid arthritis occurs when leukocytes enter the joints and release protein-chopping enzymes, oxygen radicals and other toxic factors. ( 7 )

Cell-adhesion molecules may play a role in other diseases such as spread of the cancer cells throughout the body. For example the carbohydrates recognized by ELAM-1 are expressed on different tumour cells.

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Lectins are sugar binding proteins which are abundant in living organisms from bacteria to mammals.

The mechanism of sugar binding :

Relatively low affinity binding sites for monosaccharides are formed at shallow indentations on protein surface. Selectivity is achieved through a combination of hydrogen bonding to the sugar hydroxyl groups with van der Waals packing, often against aromatic amino acid side chains. Coordination with metal ions may occasionally play a role too.

Higher selectivity is achieved by extending binding sites through additional direct and water-mediated contacts between oligosaccharides and protein surface. Dramatically increased affinity for oligosaccharides results from clustering of simple binding sites in oligomers of the lectin polypeptides. The geometry of such oligomers enables the lectins to distinguish surface arrays of polysaccharides and to cross-link glycoconjugates. ( 10 )


  1. C-type CRDs are Ca(2+)-dependent. They are involved in :
  2. I-type lectins (sialoadhesins) contain two or more I-domains ; they recognize terminal sialic acid residues. The affinity of receptor- ligand interaction is determined by the number of sialic acid residues associated with the ligand glycoprotein and by appropriate sialic acid presentation by the underlying polypeptide backbone.

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Cadherins are integral transmembrane glycoproteins which mediate Ca(2+) -dependent cell-cell adhesion among the most tissues. It is crucial for the mutual association of vertebrate cells.

For example in epithelial cells E-cadherins stabilize the junction interacting homophically with E-cadherin molecules from adjacent cells. E-cadherin adhesion system is impaired in cancer cells.Thus cancer cells can spread throughout the body.

Cadherins are associated with the actin cytoskeleton through the cytoplasmic proteins, catenins (alpha, beta and gamma=plakoglobin); beta- catenin or plakoglobin is associated directly with the cadherin and alpha- catenin is bound to beta or gamma catenin and to the actin cytoskeleton.

The anchorage of cadherins to the cytoskeleton appears to be regulated by tyrosine phosphorylation.

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Recognition and adhesion

Other functions of glycoproteins