Zinc induces structural reorganization of gelatin binding domain from human fibronectin and affects collagen binding.
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.
Graille
Marc
M
IBBMC, Université Paris 11, IFR115, CNRS UMR8619, Orsay Cedex F-91405, France. marc.graille@u-psud.fr <marc.graille@u-psud.fr>
Pagano
Maurice
M
Rose
Thierry
T
Ravaux
Michèle Reboud
MR
van Tilbeurgh
Herman
H
D002448:Cell Adhesion; D002465:Cell Movement; D003094:Collagen / Q000032:analysis / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000378:metabolism; D005353:Fibronectins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*; D005780:Gelatin / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D015032:Zinc / Q000032:analysis / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005780:Gelatin; D003094:Collagen; D015032:Zinc