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Crystal structure of a tandem pair of fibronectin type III domains from the cytoplasmic tail of integrin α6β4
Author(s) -
María de Pereda José,
Wiche Gerhard,
Liddington Robert C.
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.15.4087
Subject(s) - integrin , biology , fibronectin , hemidesmosome , microbiology and biotechnology , cytoplasm , protein subunit , integrin, beta 6 , biochemistry , cell , basement membrane , extracellular matrix , gene
The integrin α6β4 is an essential component of hemidesmosomes but it also plays a dynamic role in invasive carcinoma cells. The cytoplasmic tail of the β4 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 α6β4 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 α6β4 to be dissected at the atomic level.