Zinc induces structural reorganization of gelatin binding domain from human fibronectin and affects collagen binding.

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Graille M, Pagano M, Rose T, Ravaux MR, van Tilbeurgh H

Zinc induces structural reorganization of gelatin binding domain from human fibronectin and affects collagen binding.

Structure. 2010 Jun 9;18(6):710-8. doi: 10.1016/j.str.2010.03.012.

PubMed ID

20541508 [ View in PubMed

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Abstract

Fibronectin is a modular extracellular matrix protein involved in cell adhesion, cell motility, wound healing, and maintenance of cell morphology. It is composed of multiple repeats of three distinct modules: F(I), F(II), and F(III). Various combinations of these modules create fragments able to interact with different constituents of the extracellular matrix. Here, we present the 2.5-A resolution crystal structure of its 45-kDa gelatin-binding domain (GBD; 6F(I)-1F(II)-2F(II)-7F(I)-8F(I)-9F(I)), which also corresponds to the C-terminal half of the migration stimulating factor, a Fn splice variant expressed in human breast cancers. GBD forms a very compact zinc-mediated homodimer, in stark contrast with previous structures of fibronectin fragments. Most remarkably, 8F(I) no longer adopts the canonical F(I) fold but is composed of two long strands that associate with 7F(I) and 9F(I) into a large beta-sheet superdomain. Binding studies in solution confirmed that Zn induces conformational rearrangements and causes loss of binding of Fn-GBD to high-affinity collagen peptides. These data suggest the Zn may play a regulatory role for the cellular functions of fibronectin.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Zinc chloride	Fibronectin	Protein	Humans	Unknown	Modulator Ligand	Details
Zinc sulfate, unspecified form	Fibronectin	Protein	Humans	Unknown	Modulator Ligand	Details