They are receptor proteins that bind in the extracellular matrix to specific proteins and to other proteins in adjacent cells.
Integrins are proteins that work mechanically, joining the cell cytoskeleton to the extracellular matrix and biochemically, detecting if adhesion has occurred.
The integrin family of proteins consists of alpha and beta subtypes, which form transmembrane heterodimers.
Structure of the integrin
Each integrin heterodimer consists of an alpha (α) and beta (β) subunit associated with non-covalent interactions.
These form an extracellular ligand binding head, two multidomain “legs,” two single-pitch transmembrane helices, and two short cytoplasmic tails.
The α and β groups do not show homology to each other, however, the conserved regions are found between the subtypes of both groups.
The α-subunit leg consists of a thigh and 2 twin domains that support the ligand-binding head formed by a β-helix domain with 7 repeats that form the blades.
Some of the helix blade domains contain calcium-binding EF domains on the underside; these allosterically affect the binding ligand.
An additional αI (interactive) domain containing approximately 200 residues is present in some vertebrate α chains (nine human α subtypes) between repeats 2 and 3 of the helix.
It contains a metal ion-dependent adhesion site that is important for ligand binding.
The β subunit comprises 4 repeats of cysteine-rich epidermal growth factor, a hybrid domain (divided in sequence), a type I domain (βI), and a plexin-sempahorin-integrin domain.
Similar to αI, the βI domain contains a metal ion-dependent adhesion site for ligand binding and an additional regulatory site adjacent to the metal ion-dependent adhesion site, inhibited by Ca2 + and activated by Mn2 + for binding to the ligand.
The βI domain binds to the ligand together with the β helix or with αI (if present) through the metal ion-dependent adhesion site in a Mg2 + -dependent manner at the interface in the helmet.
While the Asp carboxyl group coordinates the βI ion the dependent adhesion site of Mg2 + metal ions, the hydrogen of the Arg side chain of the RGD ligand binds directly to Asp in domains 2 and 3 of the β helix.
They are globular domain structures of α and β subunits in a stable dimer. Ligand binding occurs at the interface of the αI or β helix and the βI domain.
Dimerization occurs across the surface of the β helix in the α chain and the hybrid domain in the β chain in the cytoplasm.
The sequences on these interacting surfaces appear to control the specificity of the strand selection.
The dimers have been shown to be stabilized and inactive by hydrophobic interactions and electrostatic salt bridges in the proximal regions of the outer and inner membrane, respectively.
The cytoplasmic tail of the β chain is known to bind to protein adapters, this activates the integrins by breaking the salt bridge between the dimer.
In general, adapter proteins promote binding to actin, however intermediate filaments have also been implicated through vimentin.
Integrins contain large (α) and small (β) subunits.
Some integrins mediate recognition and direct interactions between cells.
Integrins contain binding sites for Mg 2+ and Ca 2+ divalent cations, which are necessary for their adhesive function.
These large families of heterodimeric transmembrane glycoproteins bind cells to the extracellular matrix proteins of the basement membrane or to the ligands of other cells.
Integrins have a structural function and anchor the parent cell or another cell.
Integrins also function as adhesion receptors for extracellular ligands, they detect biochemical signals in the cell, through effector proteins.
Surprisingly, they work bi-directionally, which means that they can transmit information both outside and inside the cell.
They participate in wound healing, cell migration, and phagocytosis.
The integrin in leukocytes is primarily responsible for the adhesion of lymphocytes to the vascular endothelium and for the recruitment of leukocytes in the inflamed area.
Classification of Integrins
The differences in the beta chain of the integrins allow them to be divided into three categories: the β-1 subfamily, formed by the VLA antigens, the β-2 subfamily, formed by LFA-1, the complement receptor 3, and p150.95 , and the β-3 subfamily, consisting of glycoprotein IIb / IIIa and the vitronectin receptor.