2.0 Å Crystal Structure of a Four-Domain Segment of Human Fibronectin Encompassing the RGD Loop and Synergy Region

Abstract

We have determined the 2.0 Å crystal structure of a fragment of human fibronectin encompassing the seventh through the RGD-containing tenth type III repeats (FN7–10). The structure reveals an extended rod-like molecule with a long axis of ∼140 Å and highly variable relationships between adjacent domains. An unusually small rotation between domains 9 and 10 creates a distinctive binding site, in which the RGD loop from domain 10 and the “synergy” region from domain 9 are on the same face of FN7–10 and thus easily accessible to a single integrin molecule. The cell-binding RGD loop is well-ordered in this structure and extends ∼10 Å away from the FN7–10 core.