Hassane McHaourab

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. pmc On the origin of large flexibility of P-glycoprotein in the inward-facing state
    Po Chao Wen
    Center for Biophysics and Computational Biology, Department of Biochemistry, College of Medicine, and the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana Champaign, Urbana, Illnois 61801, USA
    J Biol Chem 288:19211-20. 2013
  2. pmc Orbital metastatic angiosarcoma
    Souhail Hassane
    Department of Ophthalmology, Mohammed V Military Teaching Hospital, University of King Mohammed V Souissi, Rabat, Morocco
    Korean J Ophthalmol 24:364-6. 2010
  3. pmc Crystal structure of an activated variant of small heat shock protein Hsp16.5
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Tennessee 37232, USA
    Biochemistry 51:5105-12. 2012
  4. pmc Toward the fourth dimension of membrane protein structure: insight into dynamics from spin-labeling EPR spectroscopy
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
    Structure 19:1549-61. 2011
  5. pmc Structure and mechanism of protein stability sensors: chaperone activity of small heat shock proteins
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232 0615, USA
    Biochemistry 48:3828-37. 2009
  6. doi request reprint Role of sequence bias in the topology of the multidrug transporter EmrE
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232 0615, USA
    Biochemistry 47:7980-2. 2008
  7. pmc Specificity of alphaA-crystallin binding to destabilized mutants of betaB1-crystallin
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
    FEBS Lett 581:1939-43. 2007
  8. ncbi request reprint Mechanism of chaperone function in small heat shock proteins. Two-mode binding of the excited states of T4 lysozyme mutants by alphaA-crystallin
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University, 741 Light Hall, Nashville, TN 37232, USA
    J Biol Chem 277:40557-66. 2002
  9. ncbi request reprint Mechanism of chaperone function in small heat-shock proteins. Fluorescence studies of the conformations of T4 lysozyme bound to alphaB-crystallin
    Hasige A Sathish
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 278:44214-21. 2003
  10. ncbi request reprint Mechanism of chaperone function in small heat shock proteins: dissociation of the HSP27 oligomer is required for recognition and binding of destabilized T4 lysozyme
    R Shashidharamurthy
    Department of Molecular Physiology and Biophysics, Vanderbilt University, 741 Light Hall, Nashville, TN 37232, USA
    J Biol Chem 280:5281-9. 2005

Research Grants

  1. MECHANISMS OF CHAPERONE FUNCTION IN THE LENS
    Hassane McHaourab; Fiscal Year: 2007
  2. Structural Dynamics of Multi-drug Resistance ABC Transporters
    Hassane McHaourab; Fiscal Year: 2007
  3. Molecular Basis for Lens Transparency
    Hassane S McHaourab; Fiscal Year: 2010
  4. Molecular Basis for Lens Transparency
    Hassane McHaourab; Fiscal Year: 2009
  5. Structural Dynamics of Multi-drug Resistance ABC Transporters
    Hassane McHaourab; Fiscal Year: 2009
  6. Molecular Basis for Lens Transparency
    Hassane McHaourab; Fiscal Year: 2009
  7. Structural Dynamics of Multi-drug Transporters
    Hassane S McHaourab; Fiscal Year: 2010
  8. Structural Dynamics of Multi-drug Resistance ABC Transporters
    Hassane McHaourab; Fiscal Year: 2007
  9. MOLECULAR BASIS OF LENS TRANSPARENCY
    Hassane McHaourab; Fiscal Year: 2007
  10. MOLECULAR BASIS OF LENS TRANSPARENCY
    Hassane McHaourab; Fiscal Year: 2003

Collaborators

  • PHOEBE STEWART
  • Kelli Kazmier
  • Jens Meiler
  • Tetsuya Mori
  • Carl Johnson
  • Martin Egli
  • Darryl Bornhop
  • Dewight R Williams
  • Hanane A Koteiche
  • Ping Zou
  • Derek P Claxton
  • M Satish Kumar
  • Marco Bortolus
  • Hasige A Sathish
  • Po Chao Wen
  • Jinhui Dong
  • Souhail Hassane
  • Sepan T Amadi
  • Ximing Qin
  • Joey C Latham
  • - Smriti
  • Nathan Alexander
  • Kavitha Surendhran
  • Peter P Borbat
  • Richard A Stein
  • Jian Shi
  • R Shashidharamurthy
  • Jack H Freed
  • Guangyong Yang
  • Petr P Borbat
  • Steven E Mansoor
  • Emad Tajkhorshid
  • Brandy Verhalen
  • Stephan Wilkens
  • MARK BYRNE
  • Naoumi Asmae
  • Elasri Fouad
  • Chana Houcine
  • Iferkhass Said
  • Oubaaz Abdelbar
  • Reda Karim
  • Sanjay Mishra
  • Ahmad Al-Mestarihi
  • Rebecca L Majdoch
  • Steve Chiu
  • Matthew D Reeves
  • David L Farrens

Detail Information

Publications33

  1. pmc On the origin of large flexibility of P-glycoprotein in the inward-facing state
    Po Chao Wen
    Center for Biophysics and Computational Biology, Department of Biochemistry, College of Medicine, and the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana Champaign, Urbana, Illnois 61801, USA
    J Biol Chem 288:19211-20. 2013
    ..The location of the protruding lipid suggests a putative pathway for direct drug recruitment from the membrane. ..
  2. pmc Orbital metastatic angiosarcoma
    Souhail Hassane
    Department of Ophthalmology, Mohammed V Military Teaching Hospital, University of King Mohammed V Souissi, Rabat, Morocco
    Korean J Ophthalmol 24:364-6. 2010
    ..Angiosarcoma was confirmed by transbronchial lung biopsy. In summary, we believed that the orbital tumour was an initial symptom of the metastasis ensuing from the lung angiosarcoma...
  3. pmc Crystal structure of an activated variant of small heat shock protein Hsp16.5
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Tennessee 37232, USA
    Biochemistry 51:5105-12. 2012
    ..5 oligomer flexibility revealed here, which is likely to be highly conserved across the sHSP superfamily, explains the relationship between oligomer expansion observed in disease-linked mutants and changes in chaperone activity...
  4. pmc Toward the fourth dimension of membrane protein structure: insight into dynamics from spin-labeling EPR spectroscopy
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
    Structure 19:1549-61. 2011
    ..Efforts to develop methods for determining structures from EPR restraints and to increase sensitivity and throughput promise to expand spin labeling applications in membrane protein structural biology...
  5. pmc Structure and mechanism of protein stability sensors: chaperone activity of small heat shock proteins
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232 0615, USA
    Biochemistry 48:3828-37. 2009
    ....
  6. doi request reprint Role of sequence bias in the topology of the multidrug transporter EmrE
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232 0615, USA
    Biochemistry 47:7980-2. 2008
    ..We propose a coupled insertion and assembly model for EmrE in which the favorable energetics of the parallel dimer interface override topological constraints arising from weak asymmetry in positive charge distribution...
  7. pmc Specificity of alphaA-crystallin binding to destabilized mutants of betaB1-crystallin
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
    FEBS Lett 581:1939-43. 2007
    ..In the lens, where alpha-crystallin binding sites are not regenerated, this may represent an added mechanism to maintain lens transparency...
  8. ncbi request reprint Mechanism of chaperone function in small heat shock proteins. Two-mode binding of the excited states of T4 lysozyme mutants by alphaA-crystallin
    Hassane S McHaourab
    Department of Molecular Physiology and Biophysics, Vanderbilt University, 741 Light Hall, Nashville, TN 37232, USA
    J Biol Chem 277:40557-66. 2002
    ..Furthermore, binding can be enhanced by increased temperature and pH, which may be reflecting conformational changes in alphaA-crystallin oligomeric structure...
  9. ncbi request reprint Mechanism of chaperone function in small heat-shock proteins. Fluorescence studies of the conformations of T4 lysozyme bound to alphaB-crystallin
    Hasige A Sathish
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 278:44214-21. 2003
    ..A high affinity binding mode to compact states may be relevant to chaperone function in the lens, where protein damage is unlikely to cause global unfolding...
  10. ncbi request reprint Mechanism of chaperone function in small heat shock proteins: dissociation of the HSP27 oligomer is required for recognition and binding of destabilized T4 lysozyme
    R Shashidharamurthy
    Department of Molecular Physiology and Biophysics, Vanderbilt University, 741 Light Hall, Nashville, TN 37232, USA
    J Biol Chem 280:5281-9. 2005
    ..Taken together, these results suggest a central role for the oligomeric equilibrium in regulating the chaperone activity of sHSP. The mutants identify sequence features important for modulating this equilibrium...
  11. pmc Structure and orientation of T4 lysozyme bound to the small heat shock protein alpha-crystallin
    Derek P Claxton
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 741 Light Hall, 2215 Garland Avenue, Nashville, TN 37232, USA
    J Mol Biol 375:1026-39. 2008
    ..Together, the structural and thermodynamic data indicate that the stably bound conformation of T4L is unfolded and support a model in which the two modes of substrate binding originate from two discrete binding sites on the chaperone...
  12. ncbi request reprint Mechanism of chaperone function in small heat-shock proteins. Phosphorylation-induced activation of two-mode binding in alphaB-crystallin
    Hanane A Koteiche
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 278:10361-7. 2003
    ....
  13. ncbi request reprint Mechanism of a hereditary cataract phenotype. Mutations in alphaA-crystallin activate substrate binding
    Hanane A Koteiche
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 281:14273-9. 2006
    ....
  14. pmc De novo high-resolution protein structure determination from sparse spin-labeling EPR data
    Nathan Alexander
    Department of Chemistry, Center for Structural Biology, Vanderbilt University, Nashville, TN 37212, USA
    Structure 16:181-95. 2008
    ..The approach can be extended to other experimental techniques such as fluorescence spectroscopy, substituted cysteine accessibility method, or mutational studies...
  15. pmc Intermolecular associations determine the dynamics of the circadian KaiABC oscillator
    Ximing Qin
    Departments of Biological Sciences and Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 107:14805-10. 2010
    ..Therefore, we report here dynamics of interaction of KaiA and KaiB with KaiC that determine the period and amplitude of this in vitro oscillator...
  16. ncbi request reprint Structural basis of energy transduction in the transport cycle of MsbA
    Jinhui Dong
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
    Science 308:1023-8. 2005
    ..These results establish the structural dynamic basis of the power stroke in multidrug-resistant ATP-binding cassette (MDR ABC) transporters...
  17. ncbi request reprint Structure of the substrate binding pocket of the multidrug transporter EmrE: site-directed spin labeling of transmembrane segment 1
    Hanane A Koteiche
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
    Biochemistry 42:6099-105. 2003
    ..and Schuldiner, S. (2000) Biochemistry 39, 14711-14719] where substrate extrusion is coupled to proton influx through electrostatic interactions and shifts of the glutamate 14 pK(a) during the cycle...
  18. pmc Structure, dynamics, and substrate-induced conformational changes of the multidrug transporter EmrE in liposomes
    Sepan T Amadi
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 285:26710-8. 2010
    ..A dynamic apo conformation is necessary for the polyspecificity of EmrE allowing the binding of structurally diverse substrates. The flexibility of TM3 may play a critical role in movement of substrates across the membrane...
  19. pmc Analysis of betaB1-crystallin unfolding equilibrium by spin and fluorescence labeling: evidence of a dimeric intermediate
    Hanane A Koteiche
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
    FEBS Lett 581:1933-8. 2007
    ..This intermediate may be a critical determinant for the life-long stability of the beta-crystallins and has important consequences on interactions with alpha-crystallin...
  20. ncbi request reprint Cryoelectron microscopy and EPR analysis of engineered symmetric and polydisperse Hsp16.5 assemblies reveals determinants of polydispersity and substrate binding
    Jian Shi
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 281:40420-8. 2006
    ..Together, these results provide a mechanistic perspective on substrate recognition and binding by the small heat shock protein superfamily...
  21. ncbi request reprint The determinants of the oligomeric structure in Hsp16.5 are encoded in the alpha-crystallin domain
    Hanane A Koteiche
    Department of Molecular Physiology and Biophysics, Vanderbilt University, 1161 21st Ave South, 741 Light Hall, Nashville, TN 37232, USA
    FEBS Lett 519:16-22. 2002
    ....
  22. pmc Free-solution label-free detection of alpha-crystallin chaperone interactions by back-scattering interferometry
    Joey C Latham
    Department of Chemistry and The Vanderbilt Institute for Chemical Biology, Vanderbilt University, VU Station B 351822, Nashville, Tennessee 37235 1822, USA
    Anal Chem 81:1865-71. 2009
    ..This work demonstrates that BSI can be extended to screen libraries of disease-related mutants to quantify changes in affinity and/or kinetics of binding...
  23. pmc Conformational cycle of the ABC transporter MsbA in liposomes: detailed analysis using double electron-electron resonance spectroscopy
    Ping Zou
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 2215 Garland Avenue, Nashville, TN 37232, USA
    J Mol Biol 393:586-97. 2009
    ..Together with extensive accessibility analysis, our results suggest that these structures capture features of the motion that couples ATP energy expenditure to work, providing a framework for the mechanism of substrate transport...
  24. pmc Elucidating the ticking of an in vitro circadian clockwork
    Tetsuya Mori
    Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America
    PLoS Biol 5:e93. 2007
    ..This study analyzes a circadian clockwork to an unprecedented level of molecular detail...
  25. doi request reprint Disulfide cross-links in the interaction of a cataract-linked alphaA-crystallin mutant with betaB1-crystallin
    M Satish Kumar
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA
    FEBS Lett 583:175-9. 2009
    ..Covalent protein cross-links are a hallmark of age-related cataract and may be a factor in its inherited form...
  26. ncbi request reprint Binding of destabilized betaB2-crystallin mutants to alpha-crystallin: the role of a folding intermediate
    Hasige A Sathish
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 279:16425-32. 2004
    ..The ability of alpha-crystallin to detect subtle changes in the population of betaB2-crystallin excited states supports a central role for this chaperone in delaying aggregation and scattering in the lens...
  27. ncbi request reprint Atomic models by cryo-EM and site-directed spin labeling: application to the N-terminal region of Hsp16.5
    Hanane A Koteiche
    Department of Molecular Physiology and Biophysics, Center for Structural Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Structure 13:1165-71. 2005
    ..By combining the EPR constraints from spin label accessibilities and proximities with the cryo-EM density, we obtained an atomic model for a portion of the Hsp16.5 N-terminal region in the context of the oligomeric complex...
  28. pmc Mapping daunorubicin-binding Sites in the ATP-binding cassette transporter MsbA using site-specific quenching by spin labels
    - Smriti
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 284:13904-13. 2009
    ..The simplest model consistent with our data has DNR entering near an elbow helix parallel to the water/membrane interface, partitioning into the open chamber, and then translocating toward the periplasm upon ATP binding...
  29. pmc Alternating access of the putative substrate-binding chamber in the ABC transporter MsbA
    Ping Zou
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 2215 Garland Avenue, Nashville, TN 37232, USA
    J Mol Biol 393:574-85. 2009
    ..The reversal in chamber hydration is likely to reduce the free energy of amphipathic substrate binding and promote translocation across the membrane...
  30. pmc Conformational motion of the ABC transporter MsbA induced by ATP hydrolysis
    Peter P Borbat
    Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York, United States of America
    PLoS Biol 5:e271. 2007
    ..Our results suggest that ATP-powered transport entails LPS sequestering into the open cytoplasmic chamber prior to its translocation by alternating access of the chamber, made possible by 10-20-A conformational changes...
  31. ncbi request reprint Protein structure determination using long-distance constraints from double-quantum coherence ESR: study of T4 lysozyme
    Petr P Borbat
    Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853 1301, USA
    J Am Chem Soc 124:5304-14. 2002
    ..This study sets the stage for the use of DQC-ESR for determining the tertiary structure of large proteins with just a small number of long-distance constraints...
  32. pmc Distance measurements by fluorescence energy homotransfer: evaluation in T4 lysozyme and correlation with dipolar coupling between spin labels
    Ping Zou
    Biophys J 92:L27-9. 2007
    ..The measurement of similar distance trends using independent probes sets the stage for the complementary use of homotransfer and dipolar coupling in the determination of static structures and detection of conformational changes...
  33. ncbi request reprint Mapping proximity within proteins using fluorescence spectroscopy. A study of T4 lysozyme showing that tryptophan residues quench bimane fluorescence
    Steven E Mansoor
    Department of Biochemistry, Oregon Health and Science University, Portland, Oregon 97201 3098, USA
    Biochemistry 41:2475-84. 2002
    ....

Research Grants33

  1. MECHANISMS OF CHAPERONE FUNCTION IN THE LENS
    Hassane McHaourab; Fiscal Year: 2007
    ..Reporter group spectroscopic approaches will be used to provide insight into the structural basis of recognition and binding. ..
  2. Structural Dynamics of Multi-drug Resistance ABC Transporters
    Hassane McHaourab; Fiscal Year: 2007
    ..Understanding their mechanisms will aid in the design of new drugs to overcome resistance to chemotherapy and the development of therapeutic strategies for the inherited pathologies. ..
  3. Molecular Basis for Lens Transparency
    Hassane S McHaourab; Fiscal Year: 2010
    ..The development of a mechanistic perspective on these molecular transformations is of fundamental biochemical importance and may well have an impact on the development of intervention and therapeutic strategies. ..
  4. Molecular Basis for Lens Transparency
    Hassane McHaourab; Fiscal Year: 2009
    ..Project Description Page 6 ..
  5. Structural Dynamics of Multi-drug Resistance ABC Transporters
    Hassane McHaourab; Fiscal Year: 2009
    ..Understanding their mechanisms will aid in the design of new drugs to overcome resistance to chemotherapy and the development of therapeutic strategies for the inherited pathologies. ..
  6. Molecular Basis for Lens Transparency
    Hassane McHaourab; Fiscal Year: 2009
    ..The development of a mechanistic perspective on these molecular transformations is of fundamental biochemical importance and may well have an impact on the development of intervention and therapeutic strategies. ..
  7. Structural Dynamics of Multi-drug Transporters
    Hassane S McHaourab; Fiscal Year: 2010
    ..These are fundamental information for the development of new therapeutic strategies to combat the evolving epidemic of drug resistance and overcome tumor resistance to chemotherapy. ..
  8. Structural Dynamics of Multi-drug Resistance ABC Transporters
    Hassane McHaourab; Fiscal Year: 2007
    ..Understanding their mechanisms will aid in the design of new drugs to overcome resistance to chemotherapy and the development of therapeutic strategies for the inherited pathologies. ..
  9. MOLECULAR BASIS OF LENS TRANSPARENCY
    Hassane McHaourab; Fiscal Year: 2007
    ..The anticipated results will elucidate common molecular events associated with these diseases. ..
  10. MOLECULAR BASIS OF LENS TRANSPARENCY
    Hassane McHaourab; Fiscal Year: 2003
    ..The anticipated results will elucidate common molecular events associated with these diseases. ..
  11. MECHANISMS OF CHAPERONE FUNCTION IN THE LENS
    Hassane McHaourab; Fiscal Year: 2003
    ..They will also elucidate, in a structural and dynamic context, the distinct roles of alphaA- and alphaB- crystallin, a critical step in the process of understanding the biophysics and biochemistry of lens transparency. ..
  12. MOLECULAR BASIS OF LENS TRANSPARENCY
    Hassane McHaourab; Fiscal Year: 2006
    ..The anticipated results will elucidate common molecular events associated with these diseases. ..
  13. Structural Dynamics of Multi-drug Transporters
    Hassane S McHaourab; Fiscal Year: 2010
    ..These are fundamental information for the development of new therapeutic strategies to combat the evolving epidemic of drug resistance and overcome tumor resistance to chemotherapy. ..