Roberto Dominguez

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. ncbi request reprint Crystal structure of the actin-binding domain of alpha-actinin 1: evaluating two competing actin-binding models
    Emma Borrego-Diaz
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    J Struct Biol 155:230-8. 2006
  2. pmc Structural insights into de novo actin polymerization
    Roberto Dominguez
    Department of Physiology, 3700 Hamilton Walk, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6085, USA
    Curr Opin Struct Biol 20:217-25. 2010
  3. ncbi request reprint The beta-thymosin/WH2 fold: multifunctionality and structure
    Roberto Dominguez
    Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104, USA
    Ann N Y Acad Sci 1112:86-94. 2007
  4. pmc Actin filament nucleation and elongation factors--structure-function relationships
    Roberto Dominguez
    Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6085, USA
    Crit Rev Biochem Mol Biol 44:351-66. 2009
  5. pmc Actin structure and function
    Roberto Dominguez
    Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6085, USA
    Annu Rev Biophys 40:169-86. 2011
  6. pmc Structural basis for the recruitment of profilin-actin complexes during filament elongation by Ena/VASP
    Francois Ferron
    Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    EMBO J 26:4597-606. 2007
  7. pmc Crystal structure of the actin-binding domain of alpha-actinin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis
    Sung Haeng Lee
    University of Pennsylvania School of Medicine, Department of Physiology, 3700 Hamilton Walk, Philadelphia, PA 19104 6085, USA
    J Mol Biol 376:317-24. 2008
  8. pmc Structure-function study of the N-terminal domain of exocyst subunit Sec3
    Kyuwon Baek
    Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 285:10424-33. 2010
  9. pmc Mechanism of actin filament nucleation by Vibrio VopL and implications for tandem W domain nucleation
    Suk Namgoong
    Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Nat Struct Mol Biol 18:1060-7. 2011
  10. pmc Structure of a longitudinal actin dimer assembled by tandem w domains: implications for actin filament nucleation
    Grzegorz Rebowski
    Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104 6085, USA
    J Mol Biol 403:11-23. 2010

Research Grants

  1. Structure of the Smooth Muscle Myosin Phosphatase
    Roberto Dominguez; Fiscal Year: 2007
  2. Structural Basis of Actin Cytoskeleton Dynamics
    Roberto Dominguez; Fiscal Year: 2010
  3. Structural Basis of Actin Cytoskeleton Dynamics
    Roberto Dominguez; Fiscal Year: 2009
  4. ATOMIC STRUCTURE OF SMOOTH MUSCLE CALDESMON
    Roberto Dominguez; Fiscal Year: 2004
  5. BAR proteins linking membrane and cytoskeleton dynamics
    Roberto Dominguez; Fiscal Year: 2010

Collaborators

Detail Information

Publications32

  1. ncbi request reprint Crystal structure of the actin-binding domain of alpha-actinin 1: evaluating two competing actin-binding models
    Emma Borrego-Diaz
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    J Struct Biol 155:230-8. 2006
    ....
  2. pmc Structural insights into de novo actin polymerization
    Roberto Dominguez
    Department of Physiology, 3700 Hamilton Walk, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6085, USA
    Curr Opin Struct Biol 20:217-25. 2010
    ..Filament nucleation and elongation factors frequently interact with Rho-family GTPases, which relay signals from membrane receptors to regulate actin cytoskeleton remodeling...
  3. ncbi request reprint The beta-thymosin/WH2 fold: multifunctionality and structure
    Roberto Dominguez
    Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104, USA
    Ann N Y Acad Sci 1112:86-94. 2007
    ....
  4. pmc Actin filament nucleation and elongation factors--structure-function relationships
    Roberto Dominguez
    Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6085, USA
    Crit Rev Biochem Mol Biol 44:351-66. 2009
    ..In contrast, the elongation function among W-based nucleators has been "outsourced" to a dedicated family of proteins, Eva/VASP, which are related to WASP-family NPFs...
  5. pmc Actin structure and function
    Roberto Dominguez
    Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6085, USA
    Annu Rev Biophys 40:169-86. 2011
    ..Here we review structures of G-actin and F-actin and discuss some of the interactions that control the polymerization and disassembly of actin...
  6. pmc Structural basis for the recruitment of profilin-actin complexes during filament elongation by Ena/VASP
    Francois Ferron
    Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    EMBO J 26:4597-606. 2007
    ..The actin monomer bound at the GAB domain is proposed to be in position to join the barbed end of the growing filament concurrently with the release of profilin...
  7. pmc Crystal structure of the actin-binding domain of alpha-actinin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis
    Sung Haeng Lee
    University of Pennsylvania School of Medicine, Department of Physiology, 3700 Hamilton Walk, Philadelphia, PA 19104 6085, USA
    J Mol Biol 376:317-24. 2008
    ..The absence of a structural change suggests that the compact ABD conformation observed in the majority of the structures is highly stable and is preserved in solution, even in FSGS mutant ABDs...
  8. pmc Structure-function study of the N-terminal domain of exocyst subunit Sec3
    Kyuwon Baek
    Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 285:10424-33. 2010
    ..Through its ability to bind the small GTPase Cdc42 and phospholipids, the PH domain of Sec3 functions as a coincidence detector at the plasma membrane...
  9. pmc Mechanism of actin filament nucleation by Vibrio VopL and implications for tandem W domain nucleation
    Suk Namgoong
    Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Nat Struct Mol Biol 18:1060-7. 2011
    ..Combined, the results suggest that VopL stabilizes a hexameric double-stranded pointed end nucleus. Analysis of hybrid constructs of VopL and the eukaryotic nucleator Spire suggest that Spire may also function as a dimer in cells...
  10. pmc Structure of a longitudinal actin dimer assembled by tandem w domains: implications for actin filament nucleation
    Grzegorz Rebowski
    Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104 6085, USA
    J Mol Biol 403:11-23. 2010
    ..We finally show that the simple addition of the C-terminal pointed end-capping helix of thymosin β4 to tandem W domains can change their activity from actin filament nucleation to monomer sequestration...
  11. pmc Mechanism of actin filament bundling by fascin
    Silvia Jansen
    Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 286:30087-96. 2011
    ..These molecules could guide the rational design of new anticancer fascin inhibitors...
  12. pmc Modulation of actin structure and function by phosphorylation of Tyr-53 and profilin binding
    Kyuwon Baek
    Department of Physiology, 3700 Hamilton Walk, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6085, USA
    Proc Natl Acad Sci U S A 105:11748-53. 2008
    ..As a result, the nucleotide cleft becomes moderately more open in the profilin-actin complex, probably explaining the stimulation of nucleotide exchange on actin by profilin...
  13. pmc X-ray scattering study of actin polymerization nuclei assembled by tandem W domains
    Grzegorz Rebowski
    Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 105:10785-90. 2008
    ..The successful stabilization of filament-like multiactin assemblies opens the way to the crystallographic investigation of intersubunit contacts in the actin filament...
  14. pmc X-ray scattering study of activated Arp2/3 complex with bound actin-WCA
    Malgorzata Boczkowska
    Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, A507 Richards Building, Philadelphia, PA 19104 6085, USA
    Structure 16:695-704. 2008
    ..The results support a model of activation that is consistent with most of the biochemical observations...
  15. pmc Large nucleotide-dependent conformational change in Rab28
    Sung Haeng Lee
    Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, A507 Richards Building, Philadelphia, PA 19104 6085, USA
    FEBS Lett 582:4107-11. 2008
    ..The double-glycine motif, which is conserved in the Arf family, only occurs in Rab28 and Rab7B of the Rab family, and may have a profound effect on their catalytic activities...
  16. pmc Structural basis for the actin-binding function of missing-in-metastasis
    Sung Haeng Lee
    Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104, USA
    Structure 15:145-55. 2007
    ..The WH2 of MIM is longer than the prototypical WH2, interacting with all four subdomains of actin. We characterize a similar WH2 at the C terminus of IRSp53 and propose that in these two proteins WH2 performs a scaffolding function...
  17. pmc Toxofilin from Toxoplasma gondii forms a ternary complex with an antiparallel actin dimer
    Sung Haeng Lee
    Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104 6085, USA
    Proc Natl Acad Sci U S A 104:16122-7. 2007
    ..This effect is linked to the formation of the antiparallel actin dimer because a construct lacking helices 1 and 2 binds only one actin and inhibits nucleotide exchange less potently...
  18. pmc Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism
    Yadaiah Madasu
    Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 110:E2677-86. 2013
    ..Sca2's α-helical fold is unusual among Gram-negative autotransporters, which overwhelmingly fold as β-solenoids. Rickettsia has therefore "rediscovered" formin-like actin nucleation and elongation. ..
  19. pmc Mechanisms of plasma membrane targeting of formin mDia2 through its amino terminal domains
    Roman Gorelik
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Biol Cell 22:189-201. 2011
    ..These results suggest that the entire N terminus of mDia2 serves as a coincidence detection module, directing mDia2 to the plasma membrane through interactions with phospholipids and activated Rif...
  20. ncbi request reprint Crystal structure of monomeric actin in the ATP state. Structural basis of nucleotide-dependent actin dynamics
    Philip Graceffa
    Boston Biomedical Research Institute, Watertown, Massachusetts 02472, USA
    J Biol Chem 278:34172-80. 2003
    ..An analysis of the existing structures of members of the actin superfamily suggests that the cleft is open in the nucleotide-free state...
  21. ncbi request reprint Actin-binding proteins--a unifying hypothesis
    Roberto Dominguez
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    Trends Biochem Sci 29:572-8. 2004
    ..As the pocket remains accessible in F-actin, it is proposed that this pocket represents a primary target for F-actin-binding proteins, such as calponin-homology-related proteins and myosin...
  22. pmc Solution properties of TMR-actin: when biochemical and crystal data agree
    Roberto Dominguez
    Biophys J 85:2073-4. 2003
  23. pmc Crystal structures of the vitamin D-binding protein and its complex with actin: structural basis of the actin-scavenger system
    Ludovic R Otterbein
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    Proc Natl Acad Sci U S A 99:8003-8. 2002
    ..Formation of the strong actin-DBP complex proceeds with limited conformational changes to both proteins, demonstrating how DBP has evolved to become an effective actin-scavenger protein...
  24. ncbi request reprint Crystallization, X-ray characterization and selenomethionine phasing of Mlc1p bound to IQ motifs from myosin V
    Mohammed Terrak
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, Massachusetts 02472, USA
    Acta Crystallogr D Biol Crystallogr 58:1882-5. 2002
    ..The other two structures (Mlc1p-IQ2 and Mlc1p-IQ3) were determined by molecular replacement using the partially refined structure of Mlc1p-IQ2,3 as a search model...
  25. pmc Two distinct myosin light chain structures are induced by specific variations within the bound IQ motifs-functional implications
    Mohammed Terrak
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    EMBO J 22:362-71. 2003
    ..The resulting 'free' N-lobes of myosin light chains in the extended conformation could mediate the formation of ternary complexes during protein localization and/or partner recruitment...
  26. ncbi request reprint Structural basis of protein phosphatase 1 regulation
    Mohammed Terrak
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, Massachusetts 02472, USA
    Nature 429:780-4. 2004
    ..The structure has general implications for the control of PP1 activity by other regulatory subunits...
  27. pmc Structure of the light chain-binding domain of myosin V
    Mohammed Terrak
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    Proc Natl Acad Sci U S A 102:12718-23. 2005
    ..The model points to a prominent role of the LCBD in the function, regulation, and molecular interactions of myosin V...
  28. pmc Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly
    David Chereau
    Boston Biomedical Research Institute, Watertown, MA 02472, USA
    Proc Natl Acad Sci U S A 102:16644-9. 2005
    ..The structures also suggest a mechanism for how profilin-binding Pro-rich sequences positioned N-terminal to WH2 could feed actin monomers directly to WH2, thereby playing a role in filament elongation...
  29. ncbi request reprint Understanding the role of the G-actin-binding domain of Ena/VASP in actin assembly
    David Chereau
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    J Struct Biol 155:195-201. 2006
    ..Conserved domain architecture suggests that WASP may work similarly...
  30. ncbi request reprint Cortactin binding to F-actin revealed by electron microscopy and 3D reconstruction
    Kiran Pant
    Department of Physiology and Biophysics, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA
    J Mol Biol 359:840-7. 2006
    ..In addition, cortactin may act as a structural adapter protein, stabilizing nascent filament branches while mediating the simultaneous recruitment of Arp2/3 and WASP...
  31. pmc Leiomodin is an actin filament nucleator in muscle cells
    David Chereau
    Boston Biomedical Research Institute, Watertown, MA 02472, USA
    Science 320:239-43. 2008
    ..Knocking down leiomodin severely compromised sarcomere assembly in cultured muscle cells, which suggests a role for leiomodin in the nucleation of tropomyosin-decorated filaments in muscles...
  32. ncbi request reprint Crystal structures of S100A6 in the Ca(2+)-free and Ca(2+)-bound states: the calcium sensor mechanism of S100 proteins revealed at atomic resolution
    Ludovic R Otterbein
    Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    Structure 10:557-67. 2002
    ..The structures have important implications for our understanding of target binding and cooperativity of Ca(2+) binding in the S100 family...

Research Grants20

  1. Structure of the Smooth Muscle Myosin Phosphatase
    Roberto Dominguez; Fiscal Year: 2007
    ..This knowledge will prove invaluable for the development of new drugs to treat cardiovascular diseases such as hypertension. ..
  2. Structural Basis of Actin Cytoskeleton Dynamics
    Roberto Dominguez; Fiscal Year: 2010
    ..The knowledge gained here will be of great relevance to understanding the molecular mechanisms of disease. ..
  3. Structural Basis of Actin Cytoskeleton Dynamics
    Roberto Dominguez; Fiscal Year: 2009
    ..By studying these motifs in parallel we will establish common and distinctive features of their structures and interactions with G- and F-actin that determine their functions in the regulation of the cytoskeleton. ..
  4. ATOMIC STRUCTURE OF SMOOTH MUSCLE CALDESMON
    Roberto Dominguez; Fiscal Year: 2004
    ....
  5. BAR proteins linking membrane and cytoskeleton dynamics
    Roberto Dominguez; Fiscal Year: 2010
    ..PICK1, in particular, is a recognized drug target, and has been implicated in long-term depression, such that knowledge of it structure may have a potential impact on human health. ..