Cortactin adopts a globular conformation and bundles actin into sheets.
Cortactin is a filamentous actin-binding protein that plays a pivotal role in translating environmental signals into coordinated rearrangement of the cytoskeleton. The dynamic reorganization of actin in the cytoskeleton drives processes including changes in cell morphology, cell migration, and phagocytosis. In general, structural proteins of the cytoskeleton bind in the N-terminal region of cortactin and regulatory proteins in the C-terminal region. Previous structural studies have reported an extended conformation for cortactin. It is therefore unclear how cortactin facilitates cross-talk between structural proteins and their regulators. In the study presented here, circular dichroism, chemical cross-linking, and small angle x-ray scattering are used to demonstrate that cortactin adopts a globular conformation, thereby bringing distant parts of the molecule into close proximity. In addition, the actin bundling activity of cortactin is characterized, showing that fully polymerized actin filaments are bundled into sheet-like structures. We present a low resolution structure that suggests how the various domains of cortactin interact to coordinate its array of binding partners at sites of actin branching.
Cowieson
Nathan P
NP
Institute for Molecular Bioscience and Australian Research Council (ARC) Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane QLD 4072 Australia.
King
Gordon
G
Cookson
David
D
Ross
Ian
I
Huber
Thomas
T
Hume
David A
DA
Kobe
Bostjan
B
Martin
Jennifer L
JL
D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000378:metabolism; D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D048430:Cell Shape / Q000502:physiology; D002942:Circular Dichroism / Q000379:methods; D051356:Cortactin / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D010587:Phagocytosis / Q000502:physiology; D020836:Protein Structure, Quaternary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology
D000199:Actins; D051356:Cortactin; C495869:Cttn protein, mouse