UCLA Chemistry and Biochemistry
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Wayne Hubbell, Ph.D.

Work Email Address:

hubbellw@jsei.ucla.edu

Laboratory Address:

JSEI BH-973

Office Address:

JSEI 3-219

Work Phone Number:

(310) 206-8830
(310) 206-8831
Distinguished Professor
Chemistry and Biochemistry, Biochemistry
Member
ACCESS Program: Depts. of Biochemistry & Molecular Biology, Brain Research Institute

A Short Biography:

Professor Hubbell received his B.S. degree in Chemistry at Oregon State University in 1965 and his Ph.D. in Chemistry at Stanford University in 1970. After completing a postdoctoral fellowship at Stanford, he joined the faculty of the Department of Chemistry at UC Berkeley. In 1983, he moved his laboratory to the Jules Stein Eye Institute at UCLA.

Awards and Honors:

University of Pécs, Hungary Honorary Degree ; National Academy of Sciences Fellow ; American Academy of Arts and Sciences Fellow ; Biophysical Society Fellow ; International EPR Society Gold Medal ; Gordon Research Conferences Alexander M. Cruickshank Lecturer ; Alcon Research Institute Award ; Biophysical Society Elisabeth Roberts Cole Award ; NIH MERIT Award ; Research to Prevent Blindness Senior Investigator Award ; Camille and Henry Dreyfus Foundation Teacher-Scholar Award ; Stanford University AFORSR-NRC Postdoctoral Fellow, Chemistry ; Intl. EPR Symposium Piette Lecture ; Burnham Institute Distinguished Lecture ; Alfred P. Sloan Foundation Fellow

Research Interest:

Dr. Hubbell's research is focused on understanding the inter-relationship of protein structure, dynamics and function. Of particular interest are proteins involved in visual signal transduction (rhodopsin, the G-protein transducin and arrestin) and soluble ligand-binding proteins. To explore functional protein dynamics in such complex systems, his laboratory has pioneered the technique of "Site-Directed Spin Labeling" (SDSL) in which a paramagnetic nitroxide side chain (R1) is introduced into the protein as a molecular sensor. The technique exploits the sensitivity of Electron Paramagnetic Resonance (EPR) to motions of R1 in the biologically important nanosecond and microsecond time domains that correspond to backbone fluctuations and conformational switching, respectively. Research in the group involves a parallel development of new EPR and SDSL technology and applications to the systems mentioned above.


Detailed Biography:

During his graduate and postdoctoral work with Harden McConnell at Stanford University, Wayne Hubbell used spin label technology to first describe the fluidity and fluidity gradient in biological membranes, landmark discoveries of broad impact in cell and membrane biology.

In 1970, he joined the faculty of the Department of Chemistry at UC Berkeley where his laboratory designed new surfactants, pioneered the molecular characterization of reconstituted membrane proteins, and developed a series of unique spin label probes to study membrane electrostatics.

In 1983, Prof. Hubbell moved his laboratory to UCLA where he became the first Jules Stein Professor of Ophthalmology and Professor of Chemistry and Biochemistry. Soon after arriving, he combined unrelated technical advancements in molecular biology and EPR spectroscopy and pioneered the powerful new technology of site-directed spin labeling (SDSL) for the determination of structure and conformational dynamics in both soluble and membrane proteins.

For his development and application of SDSL, Prof. Hubbell has received numerous honors and awards including the Gold Medal of the International EPR/ESR Society, the International Zavoisky Award from the Physical Technical Institute of the Russian Academy of Sciences, the Bruker Prize from the Royal Society of Chemistry-ESR Group, and the Elisabeth Roberts Cole from the Biophysical Society (US). He is a member of the National Academy of Sciences, American Academy of Arts and Sciences, elected to the first class of fellows of the Biophysical Society and recipient of an honorary doctorate from the University of Pécs, Hungary.

Publications:

Scoville D, Stamm JD, Altenbach C, Shvetsov A, Kokabi K, Rubenstein PA, Hubbell WL, Reisler E.   Effects of binding factors on structural elements in F-actin. Biochemistry, 2009; 48(2): 370-8.
Hanson SM, Dawson ES, Francis DJ, Van Eps N, Klug CS, Hubbell WL, Meiler J, Gurevich VV   A model for the solution structure of the rod arrestin tetramer. Structure, 2008; 16(6): 924-34.
Altenbach C, Kusnetzow AK, Ernst OP, Hofmann KP, Hubbell WL   High-resolution distance mapping in rhodopsin reveals the pattern of helix movement due to activation. Proc Natl Acad Sci USA, 2008; 105(21): 7439-44.
Hanson SM, Vishnivetskiy SA, Hubbell WL, Gurevich VV   Opposing effects of inositol hexakisphosphate on rod arrestin and arrestin2 self-association. Biochemistry, 2008; 47(3): 1070-5.
Schwartz TW, Hubbell WL.   Structural biology: A moving story of receptors. Nature, 2008; 455(7212): 473-4.
Vamvouka M, Cieslak J, Van Eps N, Hubbell W, Gross A   The structure of the lipid embedded potassium channel voltage sensor determined by double-electron-electron resonance spectroscopy. Protein Sci, 2008; 17(3): 506-17.
J. Sasaki, B. Phillips, X. Chen, N. Van Eps, A-Lim Tsai, W. Hubbell, J. Spudich   Different dark conformations function in color-sensitive photosignaling by the sensory rhodopsin I-Htrl complex Biophys. J., 2007; 92: 4045-4053.
W. Oldham, N. Van Eps, A. Preininger, W. Hubbell and H. Hamm   Mapping allosteric connections from the receptor to the nucleotide-binding pocket of heterotrimeric G proteins Proc Natl Acad Sci, 2007; 104: 7927-7932.
Expand RF, Zhang YL, Mirzabekov T, Kagan B, Silberstein A, Hubbell WL, Expand RM, Chakraborti S, Dimitrov DS, Anderson WF, Rozenberg-Adler Y   Membrane activity of an amphiphilic alpha-helical membrane-proximal cytoplasmic domain of the MoMuLV envelope glycoprotein. Exp Mol Pathol, 2007; 84(1): 9-17.
Knierim B, Hofmann KP, Ernst OP, Hubbell WL   Sequence of late molecular events in the activation of rhodopsin Proc Natl Acad Sci USA, 2007; 104(51): 20290-5.
Z. Guo, D. Cascio, K. Hideg, T. Kalai and W. Hubbell   Structure and Interactions of Nitroxide Side-chains in T4 Lysozyme: Tertiary contact and solvent-inaccessible sites in helix G. Protein Sci, 2007; 16: 1069-1086.
Susan Hanson, N Van Eps, D Francis, S Vishnivetskiy, C Klug, W Hubbell, V Gurevich   Structure and function of the visual arrestin oligomer EMBO J, 2007; 26: 1726-1736.
Smirova I, Kasho V, Choe JY, Altenbach C, Hubbell WL, Kaback HR   Sugar binding induces an outward facing conforamtion of LacY, Proc Natl Acad Sci USA, 2007; 104(42): 16504-9.
N Van Eps , W Oldham , H Hamm, W Hubbell   Structural and dynamical changes in an alpha-subunit of a hetertrimic G-protein along the activation pathway. Proc Natl Acad Sci, 2006; 44: 16194-16199.
A. Shvetsov, J. Stamm, M. Phillips, C. Altenbach, P. Rubenstein, K. Hideg, W. Hubbell, E. Reisler   Conformational Dynamics of Loop 262-274 in G- and F-actin Biochemistry, 2006; 45: 6541-6549.
A Kusnetzow, C Altenbach, and W Hubbell   Conformational states and dynamics of rhodopsin in micelles and bilayers Biochemistry, 2006; 45: 5538-5550.
K Jacobsen, W Hubbell, O Ernst, and T Risse   Details of the Partial Unfolding of T4 Lysozyme on quartz using site-directed spin labelling Angew Chem Int Ed, 2006; 45: 3874-3877.
S Hanson, D Francis, S Vishnivetskiy, E Kolobova, W Hubbell, C Klug, V. Gurevich   Differential interaction of spin labeled arrestin with inactive and active phosphorhodopsin. Proc. Natl. Acad. Sci , 2006; 103: 4900-4905.
Damon Scoville, John D. Stamm, Dora Toledo-Warshaviak, Christian Altenbach, Martin Phillips, Alexander Shvetsov, Peter A. Rubenstein, Wayne L. Hubbell, and Emil Reisler   Hydrophobic loop dynamics and actin filament stability. Biochemistry, 2006; 45: 13576-84.
J. Crane, C. Mao, A. Lilly, V. Smith, Y. Suo, W. Hubbell, L. Randall   Mapping of the docking of SecA onto the chaperone SecB by site-directed spin labeling: insight into the mechanism of ligand transfer during protein export. J Mol Biol, 2006; 353: 295-307.
W. Oldham, N. Van Eps, W. Hubbell, H. Hamm   Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nat Struct Biol, 2006; 13: 772-777.
Q. Cai, A. Kusnetzow, W. Hubbell, I. Haworth, G. Gacho, N. Van Eps, K. Hideg, E. Chambers, and P. Qin   Site-directed spin labeling measurements of nanometer distances in nucleic acids using a sequence-independent nitroxide probe. Nucleic Acids Res, 2006; 34: 4722-4730.
J. Crane, Y. Suo1, A. Lilly, C. Mao, W. Hubbell, and L. Randall   Sites of interaction of a precursor polypeptide on the export chaperone SecB mapped by site-directed spin labeling. , J Mol Biol, 2006; 363: 63-74.
J. Pyka, J. Ilnicki, C. Altenbach, W. Hubbell and W. Froncisz   Accessibility and dynamics of nitroxide side chains in T4 lysozyme measured by saturation recovery EPR. Biophys J, 2005; 89: 2059-2068.
C. Altenbach, W. Froncisz, R. Hemker, H. Mchaourab, W. Hubbell   Accessibility of nitroxide side chains: Absolute Heisenberg exchange rates from power saturation EPR. Biophys J, 2005; 89: 2103-2112.
C. Klug, T. Camenisch, W. Hubbell, J. Hyde   Multiquantum EPR spectroscopy of spin labeled arrestin K267C at 35 GHz. Biophys. J, 2005; 88: 3641-3647.
Z. Lian, Y. Lou, J. Freed, L. Columbus, W. Hubbell   A multifrequency electron spin resonance study of spin labeled T4 lysozyme dynamics using the slowly relaxing local structure model. J. Phys. Chem B, 2004; 108: 17649-17659.
J. Kim, C. Altenbach, M. Kono, D. Oprian, W. Hubbell, H.G. Khorana   Structural origins of constitutive activation in Rhodopsin: role of the K296/E113 salt bridge Proc. Natl. Acad. Sci, 2004; 101: 12508-12513.
J. Isas, R. Langen, W. Hubbell, H. Haigler   Structure and dynamics of a helical hairpin that mediates calcium-dependent membrane-binding of Annexin B12. J Biol Chem, 2004; 279: 32492-32498.
Peter Z. Qin, K Hideg, Juli Feigon, and Wayne L. Hubbell   Monitoring RNA base structure and dynamics using site-directed spin labeling Biochemistry, 2003; 42: 6772-6783.
Jeffrey H. Zhang, Gaoping Xiao, Robert P. Gunsalus and Wayne L. Hubbell   Phosphorylation triggers domain separation in the DNA binding response regulator Biochemistry, 2003; 42: 2552-2559.
T. Risse, W. Hubbell, J. Isas, H. Haiger   Structure and dynamics of proteins on planar surfaces: Annexin 12 as an exploratory example. Phys. Rev. Lett, 2003; 91: 188101.
T. Kalai, J. Jeko, W. Hubbell, K. Hideg   Synthesis of 2,2- and 2,5-disubstituted 1-oxyl pyrrolidine radicals as new homobifunctional cross-linking spin labels Synthesis , 2003; 13: 2084-2088.
A. Preininger, N. Van Eps, N.-J. Yu, M. Medkova, W. Hubbell and H. Hamm   The myristoylated amino terminus of Galpha(i)(1) plays a critical role in the structure and function of Galpha(i)(1) subunits in solution. Biochemistry, 2003; 42: 7931-7941.
M. Sutton, A. Guzzo, I. Narumi, M. Costanzo, C. Altenbach, A. Ferentz, W. Hubbell and G. Walker   A model for the structure of the Escherichia coli SOS-Regulated UmuD2 protein. DNA Repair, 2002; 1: 77-93.
L. Columbus and W. Hubbell   A new spin on protein dynamics. TiBS, 2002; 27: 288-295.
Serag AA, Altenbach C, Gingery M, Hubbell WL, Yeates TO   Arrangement of subunits and ordering of beta-strands in an amyloid sheet. Nature Struct Biol, 2002; 9: 734-739.
M. Medkova, A. Preininger, NJ Yu, W.L. Hubbell, H. Hamm   Conformational changes in the amino terminal helix of the G protein alpha subunit following dissociation from Gbetagamma subuni. Biochemistry, 2002; 41: 9962-72.
T. Kalai, M. Balog, J. Jeko, W. Hubbell and K. Hideg   Palladium-catalysed coupling reactions of paramagnetic vinyl halides Synthesis , 2002; 16: 2365-2372.
A. Barnakov, C. Altenbach, L. Barnakova, W. Hubbell, G. Hazelbauer   Site-directed spin labeling of a bacterial chemoreceptor reveals a dynamic, loosely packed transmembrane domain. Protein Sci, 2002; 11: 1472-1481.
J. Isas, R. Langen, H. Haigler, and W. Hubbell   Structure and dynamics of a helical hairpin and loop region in annexin 12: A site-directed spin labeling study. Biochemistry, 2002; 41: 1464-1473.
Columbus, L., Kalai, T., Jeko, J., Hideg, K., Hubbell, W.   Molecular motion of spin labeled side chains in alpha-helices: analysis by variation of side chain structure. Biochemistry, 2001; 40: 3828-3846.
Qin, P., Butcher, S., Feigon, J., Hubbell, W.   Quantative analysis of the isolated GAAA tetraloop/receptor interaction in solution: A site-directed spin labeling study. Biochemistry, 2001; 40: 6929-6936.
Hubbell, W., Cafiso, D., Altenbach, C.   Identifying conformational changes with site-directed spin labeling. Nature Struct. Biol., 2000; 7: 735-739.
Kim, J.-M., Altenbach, C., Thurmond, R., Khorana, H.G., Hubbell, W.   Structure and function of rhodopsin: rhodopsin mutants with a neutral amino acid at E134 have a partially activated conformation in the dark. Proc. Natl. Acad. Sci., 1997; 94: 14273-14278.
Oh, K.-J., Zhan, C., Cui, C., Hideg, K., Collier, R.J., Hubbell, W.L.   Organization of the T domain of diphtheria toxin in membranes: a site-directed spin labeling study. Science, 1996; 273: 810-812.
Hubbell, W., Mchaourab, H., Altenbach, C. and Lietzow, M.   Watching your protein move using site-directed spin labeling. Structure, 1996; 4: 779-783.
Scoville Damon, Stamm John D, Altenbach Christian, Shvetsov Alexander, Kokabi Kaveh, Rubenstein Peter A, Hubbell Wayne L, Reisler Emil   Effects of binding factors on structural elements in F-actin. Biochemistry, 2009; 48(2): 370-8.
Schwartz Thue W, Hubbell Wayne L   Structural biology: A moving story of receptors. Nature, 2008; 455(7212): 473-4.
Van Eps N Oldham WM Hamm HE Hubbell WL   Structural and dynamical changes in an alpha-subunit of a heterotrimeric G protein along the activation pathway Proc Natl Acad Sci U S A, 2006; 103(44): 16194-9.
Barnakov, A Altenbach, C Barnakova, L Hubbell, WL Hazelbauer, GL   Site-directed spin labeling of a bacterial chemoreceptor reveals a dynamic, loosely packed transmembrane domain. Protein science : a publication of the Protein Society. , 2002; 11(6): 1472-81.
Isas, JM Langen, R Haigler, HT Hubbell, WL   Structure and dynamics of a helical hairpin and loop region in annexin 12: a site-directed spin labeling study. Biochemistry. , 2002; 41(5): 1464-73.
Altenbach, C Oh, KJ Trabanino, RJ Hideg, K Hubbell, WL   Estimation of inter-residue distances in spin labeled proteins at physiological temperatures: experimental strategies and practical limitations. Biochemistry. , 2001; 40(51): 15471-82.
Altenbach, C Oh, KJ Trabanino, RJ Hideg, K Hubbell, WL   Estimation of inter-residue distances in spin labeled proteins at physiological temperatures: experimental strategies and practical limitations. Biochemistry. , 2001; 40(51): 15471-82.
Sokal, I Li, N Klug, CS Filipek, S Hubbell, WL Baehr, W Palczewski, K   Calcium-sensitive regions of GCAP1 as observed by chemical modifications, fluorescence, and EPR spectroscopies. The Journal of biological chemistry. , 2001; 276(46): 43361-73.
Serag, AA Altenbach, C Gingery, M Hubbell, WL Yeates, TO   Identification of a subunit interface in transthyretin amyloid fibrils: evidence for self-assembly from oligomeric building blocks. Biochemistry. , 2001; 40(31): 9089-96.
Gross, A Columbus, L Hideg, K Altenbach, C Hubbell, WL   Structure of the KcsA potassium channel from Streptomyces lividans: a site-directed spin labeling study of the second transmembrane segment. Biochemistry. , 1999; 38(32): 10324-35.
Altenbach, C Klein-Seetharaman, J Hwa, J Khorana, HG Hubbell, WL   Structural features and light-dependent changes in the sequence 59-75 connecting helices I and II in rhodopsin: a site-directed spin-labeling study. Biochemistry. , 1999; 38(25): 7945-9.
Langen, R Isas, JM Hubbell, WL Haigler, HT   A transmembrane form of annexin XII detected by site-directed spin labeling. Proceedings of the National Academy of Sciences of the United States of America. , 1998; 95(24): 14060-5.
Langen, R Isas, JM Luecke, H Haigler, HT Hubbell, WL   Membrane-mediated assembly of annexins studied by site-directed spin labeling. The Journal of biological chemistry. , 1998; 273(35): 22453-7.
Farrens, DL Altenbach, C Yang, K Hubbell, WL Khorana, HG   Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Science. , 1996; 274(5288): 768-70.
Steinhoff, HJ Mollaaghababa, R Altenbach, C Hideg, K Krebs, M Khorana, HG Hubbell, WL   Time-resolved detection of structural changes during the photocycle of spin-labeled bacteriorhodopsin. Science. , 1994; 266(5182): 105-7.
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