CONFORMATIONAL FLEXIBILITY AND CRYSTALLIZATION OF TANDEMLY LINKED TYPE-III MODULES OF HUMAN FIBRONECTIN

Fibronectin is a large cell adhesion molecule that is composed of seve ral functional domains. The cell-binding domain that binds to cell sur face integrins consists of repeated homologous type III modules. In th is study, recombinant fragments from the cell-binding domain of human fibronectin that participate in a newly characterized fibronectin-fibr onectin interaction with FNIII1 were crystallized. In each case, the c rystals had more than one fibronectin fragment in the asymmetric unit. Crystals of FNIII10-11 grew in the space group C2 with a = 117.1 Angs trom, b = 38.6 Angstrom, c = 80.6 Angstrom, beta = 97.2 degrees, and t wo molecules in the asymmetric unit. These crystals diffracted to 2.5 Angstrom resolution. Fragment FNIII8-11 and a shorter fragment, FNIII8 -10, crystallized in hexagonal space groups with large unit cells and two to four molecules per asymmetric unit. Even very large crystals of these fragments did not diffract beyond 4 Angstrom. The crystal packi ng for this collection of fibronectin fragments suggests conformationa l flexibility between linked type III modules. The functional relevanc e of this flexibility for elongated versus compact models of the cell- binding domain of fibronectin is discussed.