Crystal structure of a tandem pair of fibronectin type III domains from the cytoplasmic tail of integrin alpha6beta4.
The integrin alpha6beta4 is an essential component of hemidesmosomes but it also plays a dynamic role in invasive carcinoma cells. The cytoplasmic tail of the beta4 subunit is uniquely large among integrins and includes two 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 alpha6beta4 function. The structure reveals a novel interdomain interface and candidate protein-binding sites, including a large acidic cleft formed from the surfaces of both domains and a prominent loop that is reminiscent of the RGD integrin-binding loop of fibronectin. This is the first crystal structure of either a hemidesmosome component or an integrin cytoplasmic domain, and it will enable the intracellular functions of alpha6beta4 to be dissected at the atomic level.
de Pereda
J M
JM
Department of Biochemistry, University of Leicester, Leicester LE1 7RH, UK.
Wiche
G
G
Liddington
R C
RC
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000737:chemistry*; D001483:Base Sequence; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000737:chemistry*; D017931:DNA Primers; D005353:Fibronectins / Q000737:chemistry*; D039161:Integrin alpha6beta4; D016023:Integrins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D000954:Antigens, Surface; D017931:DNA Primers; D005353:Fibronectins; D039161:Integrin alpha6beta4; D016023:Integrins