Cell Adhesion Proteins

 Cell Adhesion Proteins Background

Cell adhesion was first identified in sponges in 1907. Since then, cell adhesion has been found to be critical for cellular function and organism survival. It is seen in processes such as: inflammation, cell growth, proliferation, gene regulation, differentiation, apoptosis and migration.
Cell adhesion proteins have similar structural and functional roles throughout the eukaryote kingdom. In 1957, Moscona first found mammals and birds share similar molecular characteristics and binding sites for cell adhesion. Later, more Cell adhesion proteins in higher eukaryotes were found to share structural and functional similarities to lower organisms. However, structural flexibility of each individual Cell adhesion proteins determines the specific binding characteristics of the proteins.
Cell adhesions in higher organism are mediated by multiple systems. Study of cell adhesion in lower organisms could provide information for understanding the complexity of the adhering systems in higher organisms. For example: Drosophila melanogaster is one of the model systems to study cell adhesion. This system contains major classes of Cell adhesion proteins including Notch/Delta, immunoglobulin homologs, fasciclin IV, Fasciclin I, Leucine-rich repeat proteins (LRRS), cadherins, integrins, etc. C. elegans has simpler cell adhesion systems than Drosophila. In this system, adhesions of the neighboring cells are required for the determination of cell fate. Sexual agglutination in S. cerevisiae, a unicellular eukaryote, could be the simplest model cell adhesion system for both fungi and mammals. For example: α-agglutinin is a member of the immunoglobulin superfamily. It has sequence similarities to Cell adhesion proteins in the ALS family in yeast Candida albicans and other members in the Ig superfamily, which is one of the major classes of Cell adhesion proteins in mammalian systems.

Structural Characteristics of Cell Adhesion Proteins
Cell adhesion proteins are usually glycoproteins that mediate cell-cell and cell-extracellular matrix recognition at the extracellular surface. Most Cell adhesion proteins have similar conformations in their adhesive domains. For example: the adhesive domains of cadherin, Immunoglobulin like, fibronectin type III and EGF are predominantly β-sheet structures. The common motif involved in cell adhesion is the key barrel structure containing one or two anti-parallel β sandwiches.
Ig-like domains are a major class of key barrel domains. They have sequence similarities to the variable or constant domain of antibodies containing seven to nine anti-parallel β strands. The anti-parallel β sheets form a 3-D β-barrel. Ig-like domains are stabilized by hydrophobic core and disulfide bonds. They are divided into two major sets: Ig C-like and Ig V-like domains.
Ig C-like domains contain seven β strands arranged into two anti-parallel β-sheets: one consists of strands A, B, E and D, and the other one consists of strands G, F and C. Ig V-like domains contain nine β strands. The folding of Ig V-like domains is similar to the Ig C-like domains, except two more β strands, C’ and C”, are added in the extended GFC sheet.
The central portion of each β-sheet, the B, E and C, F β-strands, forms the structurally conserved core of the Ig fold. The edge of the sheets is flexible and the non-central strands can be shifted structurally between different sheets within the domains. This flexibility allows molecules on different cells to adopt the specific conformation required for specific adhesive binding. Therefore, even though Ig-like domains in Cell adhesion proteins share conserved conformational features, they have functional diversities. They can bind to ligands varying from small peptides to hormones, or giant proteins with different binding modes.
Cell adhesion proteins have functional diversity. Interaction of Cell adhesion proteins could be homophilic or heterophilic protein-protein interactions or protein-carbohydrate interactions. Structural changes of the Cell adhesion proteins are often related to their functional properties. 

Cell adhesion protein reference
1. Moscona A. The development in vitro of chimeric aggregates of dissociated embryonic chick and mouse cells[J]. Proceedings of the National Academy of Sciences, 1957, 43(1): 184-194.
2. Juliano R L, Haskill S. Signal transduction from the extracellular matrix[J]. Journal of Cell Biology, 1993, 120: 577-577.
3. Ruoslahti E, Reed J C. Anchorage dependence, integrins, and apoptosis[J]. Cell, 1994, 77(4): 477-478.
3. Corbin V, Michelson A M, Abmayr S M, et al. A role for the Drosophila neurogenic genes in mesoderm differentiation[J]. Cell, 1991, 67(2): 311-323.
4. Gumbiner B M. Cell adhesion: the molecular basis of tissue architecture and morphogenesis[J]. Cell, 1996, 84(3): 345-357.
5. Vaughn D E, Bjorkman P J. The (Greek) key to structures of neural adhesion molecules[J]. Neuron, 1996, 16(2): 261-273.
6. Williams A F, Barclay A N. The immunoglobulin superfamily-domains for cell surface recognition[J]. Annual review of immunology, 1988, 6(1): 381-405.
7. Bork P, Holm L, Sander C. The immunoglobulin fold: structural classification, sequence patterns and common core[J]. Journal of molecular biology, 1994, 242(4): 309-320.