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ENRIQUE M. DE LA CRUZ

We study the chemical and force-producing properties of myosin molecular motors. Myosins use the energy from a cycle of ATP hydrolysis to perform mechanical work along actin filament tracks in eukaryotic cells, and are responsible for diverse physiological processes including cell division and migration, RNA transport, and muscle contraction. Force generation and motility (work output) are coupled to chemical catalysis, and each mechanical "step" results from the enzymatic cleavage of a single ATP molecule. Although all myosins share a common catalytic ATPase cycle pathway, modulation of the rate and equilibrium constants that define the cycle confer specific physical and biochemical properties to the motor for specific physiological tasks. Some myosins have evolved for anchoring cellular structures and maintaining tension, while others are processive and individual motor molecules take multiple steps along an actin filament without detaching, enabling them to carry biological cargo over long distances.

Our research focuses on vertebrate myosins enriched in hair cells of the inner ear and in synaptic termini of neurons. Mutations in these myosins generate human diseases including Usher syndrome type 1B, the most common deafness-blindness disorder in humans, and Griscelli's syndrome, an inherited disorder characterized by severe immunodeficiency and neurological dysfunction. We use equilibrium and rapid mixing methods to measure the kinetic and thermodynamic behavior of the individual reactions in the ATPase cycle mechanism, in vitro motility assays to quantitate ATP-dependent movements of actin filaments driven by purified myosin, and single-molecule methods to assay force-generation, bond strength and processivity of individual myosin molecules. We are testing models of processive myosin motility and characterizing the molecular basis of deafness causing mutations through the generation of site-specific mutants.

We also focus on defining cooperative binding to an actin filament in quantitative terms, and identifying the thermodynamic and mechanical parameters that govern allosteric transitions in the filament lattice. This information is being used to understand how regulatory proteins destabilize and fragment actin filaments

Selected Publications

Henn A. and De La Cruz, E. M. Vertebrate myosin VIIb is a high duty ratio motor adapted for generating and maintaining tension. J. Biol. Chem. 280, 39665-39676 (2005)

Olivares, A. O., Chang, W., Mooseker, M. S., Hackney D. D. and De La Cruz, E. M. The tail domain of myosin Va modulates actin binding to one head. J. Biol. Chem. 281, 31326-31336 (2006)

Cao, W., Goodarzi, J. and De La Cruz, E. M.  Energetics and kinetics of cooperative cofilin-actin filament interactions.  J. Mol. Biol. 361, 257-267 (2006)

Henn, A., Cao, W., Hackney, D. and De La Cruz, E. M. The ATPase cycle mechanism of the DEAD-box rRNA helicase, DbpA.  J. Mol. Biol. 377, 193-205 (2008)

Frederick, K. B., Sept, D. and De La Cruz, E. M. Effects of solution crowding on actin polymerization reveal the energetic basis for nucleotide-dependent filament stability.  J. Mol. Biol. (In Press)

Last Updated 04-18-2008