Jm. De Pereda et al., Crystal structure of a tandem pair of fibronectin type III domains from the cytoplasmic tail of integrin alpha 6 beta 4, EMBO J, 18(15), 1999, pp. 4087-4095
The integrin alpha 6 beta 4 is an essential component of hemidesmosomes but
it also plays a dynamic role in invasive carcinoma cells. The cytoplasmic
tail of the beta 4 subunit is uniquely large among integrins and includes t
wo pairs of fibronectin type III domains separated by a connecting segment.
Here we describe the crystal structure of the first tandem domain pair, a
module that is critical for alpha 6 beta 4 function. The structure reveals
a novel interdomain interface and candidate protein-binding sites, includin
g a large acidic cleft formed from the surfaces of both domains and a promi
nent loop that is reminiscent of the RGD integrin-binding loop of fibronect
in. This is the first crystal structure of either a hemidesmosome component
or an integrin cytoplasmic domain, and it will enable the intracellular fu
nctions of alpha 6 beta 4 to be dissected at the atomic level.