Crystal structure of a tandem pair of fibronectin type III domains from the cytoplasmic tail of integrin alpha6beta4

EMBO J. 1999 Aug 2;18(15):4087-95. doi: 10.1093/emboj/18.15.4087.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Surface / chemistry*
  • Base Sequence
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Cytoplasm / chemistry*
  • DNA Primers
  • Fibronectins / chemistry*
  • Integrin alpha6beta4
  • Integrins / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Sequence Homology, Amino Acid


  • Antigens, Surface
  • DNA Primers
  • Fibronectins
  • Integrin alpha6beta4
  • Integrins

Associated data

  • PDB/1QG3