Feature, Structure and Classifi cation of Adhesion Molecules: An Overview - Adhesion Molecules - page 7

h e extracellular region of integrin β subunits contains a hybrid domain, a
plexin-semaphorin-integrin (PSI) domain, four epidermal growth factor (EGF)-
like repeats and a β tail domain (βTD) ( Fig. 3A ). h e hybrid domain is an Ig-
like domain comprising an αA-like motif (the βA domain) inserted between
two β-sheets. h e βA domain contains a metal-binding motif and binds divalent
cations when the α subunit does not contain an αA domain (Takada et al. 2007).
h e PSI domain forms a two-stranded anti-parallel β-sheet l anked by two short
helices and contributes to integrin activation. h e cytoplasmic tails of integrin β
chains are short and highly conserved and contain one or two phosphorylation
motifs. h e tails recruit proteins such as talin, which bind actin i laments, thus
connecting integrins to the actin cytoskeleton. Integrin-cytoskeletal interactions
are essential for all integrin-mediated functions (Takada et al. 2007).
The Integrin Heterodimer
h e extracellular structure of integrin heterodimers consists of a 'head' and
'legs. h e head, which mediates integrin-ligand interactions, is the major point
of contact between α and β subunits. Contacts are formed by interactions of the
propeller (α chain) with the βA domain (β chain) (Arnaout et al. 2007). h e legs
are formed by the h igh and Calf domains of the α subunit and the PSI, EGF
and βTD domains of the β subunit (Arnaout 2002). h e 'knee' of the α subunit
lies at the junction of the h igh and Calf-1 domains, whereas the corresponding
region of the β chain lies in the PSI-EGF-1/2 region. h e knees allows integrins
to adopt a bent or upright conformation, which is critical to integrin activation
( Fig. 3 ) (Arnaout 2002). Additional contacts between α and β subunits exist
between Calf-1 and EGF3; Calf-2 and EGF4; Calf-2 and βTD; and the α and β
cytoplasmic tails (Arnaout 2002).
Integrin-Ligand Binding
Integrins may bind divalent cations via two dif erent domains, αA and βA. h e
αA domain is found in the α chains: α1, α2, α10, α11, αM, αX, αL and αD, and
mediates cation binding when present. If the αA domain is absent, cation binding
occurs via the βA domain found in all β chains (Arnaout et al. 2007).
h e ligand-binding pocket is formed by the interface between blades 2 and
3 of the propeller domain of the α chain and the βA domain of the β chain. Its
orientation alters slightly depending on whether or not the α chain contains the
αA domain. Integrins are classii ed according to the presence or absence of the αA
domain and/or their ligands ( Fig. 4 ) . Four αA-containing α chains (α1, α2, α10 and
α11) combine with β1 to give a distinct laminin/collagen binding subfamily. h e
non αA-containing integrins (α3β1, α6β1, α7β1 and α6β4) are selective laminin
receptors and bind to a dif erent site on laminin than the αA-containing integrins