Molecular Biophysics and Biochemistry: E De La Cruz Lab
Identifying the chemical and physical principles of work production by molecular motor protein enzymes and polymers has emerged as a major area in contemporary Biochemistry and Biophysics. My research program integrates comprehensive kinetic and thermodynamic analyses of catalytic reaction pathways with computational and mathematical modeling to develop and test predictive models of work output by molecular motor proteins, enzyme function and adaptation, and biopolymer fragmentation. Our work has revealed how enzymatic adaptations among evolutionary related molecular motor proteins determine their biological function, and how cells regulate the length and assembly dynamics of polymers that drive cell movement.
Our current and future efforts focus primarily in three areas:
A) identifying the molecular origins of actin filament elasticity and the mechanical basis of filament severing by regulatory proteins;
B) defining how ATP utilization by DEAD-box proteins (DBPs) is coupled to duplex rRNA unwinding; and
C) determining the catalytic pathways, specificities and biological activities of nucleotide pyrophosphatase/phosphodiesterase (NPP) enzymes.
Extensive Research Description
Persistence software can be found on our Lab page.
- W. Cao & EM De La Cruz (2013) Quantitative full time course analysis of nonlinear enzyme cycling kinetics. Nature Scientific Reports 3, 2658. DOI:10.1038/srep02658
- H Kang, MJ Bradley, BR McCullough, A Pierre, EE Grintsevich, E Reisler & EM De La Cruz (2012) Identification of cation binding sites on actin that drive polymerization and modulate bending stiffness. Proc. Natl. Acad. Sci. 109,16923-7.
- AC Reymann, R Boujemaa-Paterski, JL Martiel, C Guérin, W Cao, HF Chin, EM De La Cruz, M Théry & L Blanchoin (2012) Actin network architecture can determine myosin motor activity. Science 336:1310-4.
- W Cao, MM Coman, S Ding, A Henn, ER Middleton, E Rhoades, DD Hackney, AM Pyle & EM De La Cruz (2011) Mechanism of Mss116 ATPase reveals functional diversity of DEAD-box proteins. J. Mol. Biol. 409, 399-414.
- BR McCullough, E Grintsevich, C Chen, H Kang, A Hutchison, A Henn, W Cao, C Suarez, J-L Martiel, JL Blanchoin, E Reisler & EM De La Cruz (2011) Modulation of actin filament flexibility promotes severing by cofilin. Biophys. J. 101, 151-9.
- A Henn, W Cao, N Licciardello, SE Heitkamp, DD Hackney & EM De La Cruz (2010) Pathway of ATP utilization and duplex rRNA unwinding by the DEAD box helicase, DbpA. Proc. Natl. Acad. Sci. 107, 4046-50. *Faculty of 1000 “Must Read”
- BR McCullough, L Blanchoin, JL Martiel & EM De La Cruz (2008) Cofilin Increases the Bending Flexibility of Actin Filaments: Implications for Severing and Cell Mechanics. J. Mol. Biol., 381, 550-558.
- LP Saunders, W Cao, WC Chang, RA Albright, DT Braddock & EM De La Cruz (2011) Kinetic analysis of autotoxin reveals substrate-specific catalytic pathways and a mechanism for lysophophatidic actin distribution. J. Biol. Chem. 286, 30130-41.
- EM De La Cruz, J Roland, BR McCullough, L Blanchoin, and J-L Martiel (2010) Origin of Twist-Bend Coupling in Actin Filaments. Biophys. J., 99:1852-1860.
- HF Chin, Y Cai, S Menon, S Ferro-Novick, KM Reinisch & EM De La Cruz (2009) Kinetic analysis of the guanine nucleotide exchange activity of TRAPP, a multimeric Ypt1p exchange factor. J. Mol. Biol. 389, 275-88.
- A Henn, W Cao, D Hackney & EM De La Cruz (2008) The ATPase cycle mechanism of the DEAD-box rRNA helicase, DbpA. J. Mol Biol. 377, 193-205.
- LP Saunders, A Ouellette, H Zhou, R Bandle, EM De La Cruz* & DT Braddock* (2008) Identification and validation of small molecule inhibitors against the prometastatic enzyme Autotaxin, a lysophospholipase D. Mol. Cancer Ther. 7, 3352-62. (*Corresponding
- Y Oguchi, SV Mikhailenko, T Ohki, AO Olivares, EM De La Cruz & S Ishiwata (2008) Common mechanochemical principles control the oppositely directed myosin motors V and VI. Proc. Natl. Acad. Sci., 105, 7714-9.
- KB Frederick, D Sept & EM De La Cruz (2008) Effects of solution crowding on actin polymerization reveal the energetic basis for nucleotide-dependent filament stability. J. Mol. Biol. 378, 540-50.
- 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)
- 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)
- MA Talavera, EE Matthews, WK Eliason, I Sagi, J Wang, A Henn & EM De La Cruz (2006) Hydrodynamic characterization of the DEAD-Box RNA Helicase DbpA. J. Mol. Biol. 355, 697-707.
- 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)
- E Prochniewicz, N Janson, DD Thomas & EM De La Cruz (2005) Cofilin increases the torsional flexibility and dynamics of actin filaments. J. Mol. Biol. 353, 990-1000.
- EM De La Cruz (2005) Cofilin binding to muscle and non-muscle actin filaments: Isoform-dependent cooperative interactions. J. Mol. Biol. 346, 557-564.
- DE Hannemann, W Cao, AO Olivares, JP Robblee & EM De La Cruz (2005) Magnesium, ADP and Actin Binding Linkage of Myosin V: Evidence for Multiple Myosin V-ADP and Actomyosin V-ADP States. Biochemistry 44, 8826-8840.
- JP Robblee, W Cao, A Henn, DE Hannemann & EM De La Cruz (2005) Thermodynamics of Nucleotide Binding to Actomyosin V and VI: A Positive Heat Capacity Change Accompanies Strong ADP Binding. Biochemistry 44, 10238-49.
- JP Robblee, AO Olivares & EM De La Cruz (2004) Mechanism of nucleotide binding to acto-myosin VI: Evidence for allosteric head-head communication.J. Biol. Chem. 279,38608-17.
- S Uemura, H Higuchi, AO Olivares, EM De La Cruz & S Ishiwata (2004) Mechanochemical coupling of two substeps in a single myosin V motor. Nat. Struct. Mol. Biol. 11,877-83.