TY - JOUR
T1 - Zinc Induces Structural Reorganization of Gelatin Binding Domain from Human Fibronectin and Affects Collagen Binding
AU - Graille, Marc
AU - Pagano, Maurice
AU - Rose, Thierry
AU - Ravaux, Michèle Reboud
AU - van Tilbeurgh, Herman
PY - 2010/6/1
Y1 - 2010/6/1
N2 - 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: FI, FII, and FIII. Various combinations of these modules create fragments able to interact with different constituents of the extracellular matrix. Here, we present the 2.5-Å resolution crystal structure of its 45-kDa gelatin-binding domain (GBD; 6FI-1FII-2FII-7FI-8FI-9FI), 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, 8FI no longer adopts the canonical FI fold but is composed of two long strands that associate with 7FI and 9FI into a large β-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.
AB - 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: FI, FII, and FIII. Various combinations of these modules create fragments able to interact with different constituents of the extracellular matrix. Here, we present the 2.5-Å resolution crystal structure of its 45-kDa gelatin-binding domain (GBD; 6FI-1FII-2FII-7FI-8FI-9FI), 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, 8FI no longer adopts the canonical FI fold but is composed of two long strands that associate with 7FI and 9FI into a large β-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.
KW - Cellbio
U2 - 10.1016/j.str.2010.03.012
DO - 10.1016/j.str.2010.03.012
M3 - Article
C2 - 20541508
AN - SCOPUS:77953566262
SN - 0969-2126
VL - 18
SP - 710
EP - 718
JO - Structure
JF - Structure
IS - 6
ER -
