STRUCTURAL BIOLOGY OF ACTIN CROSSLINKING PROTEINS

Project: Research project

Project Details

Description

DESCRIPTION: Filamentous actin assembles into a number of higher order
structures with unique physicochemical properties which control cytokinesis,
cell and substrate adhesion, pseudopod extension in chemotactic and
generalized motility, and the establishment and maintenance of cell
morphology. The formation of different actin assemblies is controller by
the specific biochemical properties of the actin crosslinking proteins which
are themselves regulated by calcium fluxes and phosphorylation events.
Thus, the crosslinking proteins make these assemblies responsive to the
immediate structural and dynamic needs of the cell.

The high resolution crystal structures of the actin crosslinking proteins,
human fimbrin, human fascin and ABP-30, in combination with biochemical
analysis, will identify which amino acids are important for binding actin
with those involved in regulation by calcium and phosphorylation. The
contributions of these residues will be tested by mutagenesis and
biochemical characterization. The in vivo importance of specific
biochemical activities will be assessed by the expression of biochemically
defined mutants in living cells. Fimbrin is involved in the life cycle of
the bacterial parasites Shigella and Listeria and is closely related to the
actin binding domain in dystrophin, the defective protein in muscular
dystrophy.

These studies will provide the first X-ray structure of an actin
crosslinking protein which will allow for an extension of existing models of
actin bundling and will provide atomic level detail about the actin binding
surfaces and the mechanisms which regulate actin assemblies. The expression
studies will show the contribution of specific crosslinker properties to the
formation and function of specific actin assemblies in vivo.
StatusFinished
Effective start/end date9/30/968/31/02

Funding

  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $251,671.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases

ASJC

  • Structural Biology
  • Biochemistry

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