Biomedical Engineering Reference
In-Depth Information
Fig. 4
h e integrin family. Lines indicate heterodimeric a-b pairings identii ed on mammalian
cells. h e lines joining a-b pairs indicate the ligands they bind: bold line, laminin/collagen
binding; dot ed line, selective laminin binding; dashed line, LDV or LEV motif binding; and
standard line, RGD binding integrins.
(Humphries
et al.
2006). h e αV-integrins, and α5β1, α8β1 and αIIbβ3, recognize
the RGD (arginine, glycine, aspartic acid) motif, which is important for integrin
binding to i bronectin, vitronectin and collagen. Although many RGD-binding
integrins interact with the same ligands, they bind with dif erent ai nities, rel ecting
the preciseness of the i t of the RGD motif with the ligand binding pockets created
by dif erent α-β chain combinations (Humphries
et al.
2006). Integrins α4β1, α4β7,
α9β1 and αEβ7 recognize an acidic motif; LDV (leucine, aspartic acid, valine)
found in i bronectin and some Ig-SF members. h e β2-integrins (αDβ2, αLβ2,
αMβ2, αXβ2) bind a similar LEV motif, where the aspartic acid (D) is replaced by
glutamate (E) (Humphries
et al.
2006).
Integrin Activation
Integrins display three major activation states: inactive (low ai nity), active (high
ai nity) and ligand occupied (Askari
et al.
2009). In the switchblade model of
binding site to be buried. Integrins are active when upright, fully exposing the
ligand-binding pocket (Shimaoka
et al.
2002, Askari
et al.
2009).
When inactive, integrins bind ligands with low ai nity. h is low-ai nity
interaction stimulates intracellular signals that activate the cytoskeletal protein
talin, which binds to the cytoplasmic tail of the β subunit. h is disrupts the
inhibitory association between the α and β chains, allows the cytoplasmic and
transmembrane regions of the two chains to separate, and leads to the extracellular
domain changing from a bent to an extended form to allow high-ai nity ligand
binding (Askari
et al.
2009).
