Vanderbilt University School of Medicine

Beth, Albert H. , Ph.D.
Professor of Molecular Physiology and Biophysics

Lab Url: N/A

Phone Number: 615-322-4235

Email Address:Al.Beth@vanderbilt.edu

Beth, Albert's picture

Office Address   Mailing Address

727-A Light Hall

727 Light Hall 0615


Research Keywords
Spectroscopy, Membrane Proteins, Band 3, EGF Receptor, Molecular Probes

Research Specialty
Structure, dynamics, and interactions of membrane proteins

Research Description
Intrinsic membrane proteins serve a number of essential functions in all cells. These functions include substrate transport, signalling, and membrane stabilization to cite a few. Despite their abundance (approximately 1/3 of the human genome), their essential functions in normal physiology, and their involvement in many diseases, relatively little is known about the structures of most membrane proteins. This is due in large part to the fact that the membrane proteins are not generally amenable to structural characterization using classical techniques such as X-ray crystallography and NMR. Our laboratory is involved in the development and application of new spectroscopic approaches to determine the structures of intrinsic membrane proteins including how structural rearrangements modulate their biological functions.

Specifically, we are employing spectroscopic techniques including electron paramagnetic resonance, nuclear magnetic resonance, and fluorescence to characterize the structure, dynamics and interactions of the anion exchange protein in human erythrocytes, the receptor for epidermal growth factor (EGF) in A-431 cells and the 5-HT3 receptor in neurons.

Specific questions currently being addressed include: What are the structures of the transmembrane and cytoplasmic domains of the anion exchange protein? What is the nature and extent of interactions between the cytoplasmic domain of the anion exchange protein and the extensive membrane skeleton and how are these interactions altered in erythrocytes exhibiting abnormal fragility from patients with hemolytic anemias? What are the oligomeric structures of the anion exchange protein and the EGF receptor in their native membranes? What molecular rearrangements occur in the EGF receptor upon EGF binding and how are these changes related temporally to activation of its tyrosine kinase activity? How are the subunits of the 5-HT3 receptor arranged and how does this structure lead to the formation of a ligand-gated ion channel? How do compounds that modeulate the function of the 5-HT3 receptor such as ethanol and anesthetics alter its structure and interactions?


Publications
DeSensi, SC, Rangel, DP, Beth, AH, Lybrand, TP, Hustedt, EJ. Simulation of nitroxide electron paramagnetic resonance spectra from brownian trajectories and molecular dynamics simulations. Biophys J, 94(10), 3798-809, 2008. PMCID:2367180

Beth, AH. How to Assemble the Parts: Structures of Protein Complexes from their Components. Biophys J, 93(10), 3339, 2007. PMCID:2072061

Zhou, Z, DeSensi, SC, Stein, RA, Brandon, S, Song, L, Cobb, CE, Hustedt, EJ, Beth, AH. Structure of the cytoplasmic domain of erythrocyte band 3 hereditary spherocytosis variant P327R: band 3 Tuscaloosa. Biochemistry, 46(36), 10248-57, 2007.

Beth, A.H., and Hustedt, E.J., (S.S. Eaton, G.R. Eaton, and L.J. Berliner, eds.). Saturation Transfer EPR: Rotational Dynamics of membrane proteins. . , (Kluwer Academic/Plenum Publishing), 369-408, 2005.

Whitson, KB, Whitson, SR, Red-Brewer, ML, McCoy, AJ, Vitali, AA, Walker, F, Johns, TG, Beth, AH, Staros, JV. Functional effects of glycosylation at Asn-579 of the epidermal growth factor receptor. Biochemistry, 44(45), 14920-31, 2005.

Zhou, Z, DeSensi, SC, Stein, RA, Brandon, S, Dixit, M, McArdle, EJ, Warren, EM, Kroh, HK, Song, L, Cobb, CE, Hustedt, EJ, Beth, AH. Solution structure of the cytoplasmic domain of erythrocyte membrane band 3 determined by site-directed spin labeling. Biochemistry, 44(46), 15115-28, 2005.

Hustedt, EJ, Beth, AH. High field/high frequency saturation transfer electron paramagnetic resonance spectroscopy: increased sensitivity to very slow rotational motions. Biophys J, 86(6), 3940-50, 2004. PMCID:1304295

Whitson, Kristin B, Beechem, Joseph M, Beth, Albert H, Staros, James V. Preparation and characterization of Alexa Fluor 594-labeled epidermal growth factor for fluorescence resonance energy transfer studies: application to the epidermal growth factor receptor. Anal Biochem, 324(2), 227-36, 2004.

Stein, Richard A, Hustedt, Eric J, Staros, James V, Beth, Albert H. Rotational dynamics of the epidermal growth factor receptor. Biochemistry, 41(6), 1957-64, 2002.

Hustedt, E.J. and Beth, A.H. (2001) The sensitivity of saturation transfer electron paramagnetic resonance spectra to restricted amplitude uniaxial rotational diffusion. Biophys. J., in press.

Blackman, S M, Hustedt, E J, Cobb, C E, Beth, A H. Flexibility of the cytoplasmic domain of the anion exchange protein, band 3, in human erythrocytes. Biophys J, 81(6), 3363-76, 2001. PMCID:1301793

Hustedt, E J, Beth, A H. The sensitivity of saturation transfer electron paramagnetic resonance spectra to restricted amplitude uniaxial rotational diffusion. Biophys J, 81(6), 3156-65, 2001. PMCID:1301776

Hustedt, E.J. and Beth, A.H. Structural information from CW-EPR spectra of dipolar-coupled nitroxide spin-labels. Biological Magnetic Resonance Volume 19, S.S. Eaton, G.R. Eaton, and L.J. Berliner, eds., Kluwer Academic/Plenum Press, New York, , 155-184, 2001.

Hustedt, E.J. and Beth, A.H. Simulation of saturation transfer electron paramagnetic resonance spectra for a restricted uniaxial rotational diffusion model. Biophys. J. , 81, 3156-3165, 2001.

Hustedt, E J, Beth, A H. Nitroxide spin-spin interactions: applications to protein structure and dynamics. Annu Rev Biophys Biomol Struct, 28, 129-53, 1999.

Blackman, S M, Piston, D W, Beth, A H. Oligomeric state of human erythrocyte band 3 measured by fluorescence resonance energy homotransfer. Biophys J, 75(2), 1117-30, 1998. PMCID:1299786

Hustedt, E J, Smirnov, A I, Laub, C F, Cobb, C E, Beth, A H. Molecular distances from dipolar coupled spin-labels: the global analysis of multifrequency continuous wave electron paramagnetic resonance data. Biophys J, 72(4), 1861-77, 1997. PMCID:1184380

Blackman, S M, Cobb, C E, Beth, A H, Piston, D W. The orientation of eosin-5-maleimide on human erythrocyte band 3 measured by fluorescence polarization microscopy. Biophys J, 71(1), 194-208, 1996. PMCID:1233471

Hustedt, E J, Beth, A H. Determination of the orientation of a band 3 affinity spin-label relative to the membrane normal axis of the human erythrocyte. Biochemistry, 35(21), 6944-54, 1996.

Scothorn, D J, Wojcicki, W E, Hustedt, E J, Beth, A H, Cobb, C E. Synthesis and characterization of a novel spin-labeled affinity probe of human erythrocyte band 3: characteristics of the stilbenedisulfonate binding site. Biochemistry, 35(21), 6931-43, 1996.

Beth, A.H. Bait region-thiol ester mapping in human a2-macroglobulin. FEBS Lett., 367, 137-140, 1995.

Hustedt, E J, Beth, A H. Analysis of saturation transfer electron paramagnetic resonance spectra of a spin-labeled integral membrane protein, band 3, in terms of the uniaxial rotational diffusion model. Biophys J, 69(4), 1409-23, 1995. PMCID:1236371

Cobb, C E, Hustedt, E J, Beechem, J M, Beth, A H. Protein rotational dynamics investigated with a dual EPR/optical molecular probe. Spin-labeled eosin. Biophys J, 64(3), 605-13, 1993. PMCID:1262372

Hustedt, E J, Cobb, C E, Beth, A H, Beechem, J M. Measurement of rotational dynamics by the simultaneous nonlinear analysis of optical and EPR data. Biophys J, 64(3), 614-21, 1993. PMCID:1262373

Rousseau, D L, Guyer, C A, Beth, A H, Papayannopoulos, I A, Wang, B, Wu, R, Mroczkowski, B, Staros, J V. Preparation and characterization of a bifunctionally spin-labeled mutant of murine epidermal growth factor for saturation-transfer electron paramagnetic resonance studies of the growth factor/receptor complex. Biochemistry, 32(31), 7893-903, 1993.

Wojcicki, W E, Beth, A H. Structural and binding properties of the stilbenedisulfonate sites on erythrocyte band 3: an electron paramagnetic resonance study using spin-labeled stilbenedisulfonates. Biochemistry, 32(36), 9454-64, 1993.

Beth, A.H., Cobb, C.E., and Beechem, J.M. Synthesis and characterization of a combined fluorescence, phosphorescence, and electron paramagnetic resonance probe. Society of Photo-Optical Instrumentation Engineers, Time-Resolved Laser Spectroscopy, 3, 504-512, 1992.

Faulkner-O'Brien, L A, Beth, A H, Papayannopoulos, I A, Anjaneyulu, P S, Staros, J V. Preparation and characterization of spin-labeled derivatives of epidermal growth factor (EGF) for investigations of the interactions of EGF with its receptor by electron paramagnetic resonance spectroscopy. Biochemistry, 30(37), 8976-85, 1991.

Harmon, C M, Luce, P, Beth, A H, Abumrad, N A. Labeling of adipocyte membranes by sulfo-N-succinimidyl derivatives of long-chain fatty acids: inhibition of fatty acid transport. J Membr Biol, 121(3), 261-8, 1991.

Cobb, C E, Beth, A H. Identification of the eosinyl-5-maleimide reaction site on the human erythrocyte anion-exchange protein: overlap with the reaction sites of other chemical probes. Biochemistry, 29(36), 8283-90, 1990.

Cobb, C E, Juliao, S, Balasubramanian, K, Staros, J V, Beth, A H. Effects of diethyl ether on membrane lipid ordering and on rotational dynamics of the anion exchange protein in intact human erythrocytes: correlations with anion exchange function. Biochemistry, 29(48), 10799-806, 1990.

Cobb, C.E., and Beth, A.H. Identification of the eosinyl-5-maleimide reaction site on the human erythrocyte anion-exchange protein: Overlap with reaction sites of other chemical probes. Biochemistry , 29, 8283-8290, 1990.

Conturo, T E, Kessler, R M, Beth, A H. Cooperative T1 and T2 effects on contrast using a new driven inversion spin-echo (DISE) MRI pulse sequence. Magn Reson Med, 15(3), 397-419, 1990.

Anjaneyulu, P S, Beth, A H, Cobb, C E, Juliao, S F, Sweetman, B J, Staros, J V. Bis(sulfo-N-succinimidyl) doxyl-2-spiro-5'-azelate: synthesis, characterization, and reaction with the anion-exchange channel in intact human erythrocytes. Biochemistry, 28(16), 6583-90, 1989.

Beth, A.H. and Robinson, B.H. Nitrogen-15 and deuterium substituted spin label for studies of very slow rotational motion. "Biological Magnetic Resonance, Vol. 8, Spin Labeling: Theory and Applications", , 8, 179-253, 1989.

Conturo, T E, Price, R R, Beth, A H. Addendum to 'rapid local rectangular views and magnifications: reduced phase encoding of orthogonally excited spin echoes'. Magn Reson Med, 9(3), 389-90, 1989.

Whitesell, R R, Regen, D M, Beth, A H, Pelletier, D K, Abumrad, N A. Activation energy of the slowest step in the glucose carrier cycle: break at 23 degrees C and correlation with membrane lipid fluidity. Biochemistry, 28(13), 5618-25, 1989.

Abumrad, N A, Briscoe, P, Beth, A H, Whitesell, R R. Temperature dependence of glucose transport in erythrocytes from normal and alloxan-diabetic rats. Biochim Biophys Acta, 938(2), 222-30, 1988.

Anjaneyulu, P S, Beth, A H, Sweetman, B J, Faulkner, L A, Staros, J V. Bis(sulfo-N-succinimidyl) [15N,2H16]doxyl-2-spiro-4'-pimelate, a stable isotope-substituted, membrane-impermeant bifunctional spin label for studies of the dynamics of membrane proteins: application to the anion-exchange channel in intact human erythrocytes. Biochemistry, 27(18), 6844-51, 1988.

Conturo, T E, Price, R R, Beth, A H. Rapid local rectangular views and magnifications: reduced phase encoding of orthogonally excited spin echoes. Magn Reson Med, 6(4), 418-29, 1988.

Correia, J J, Beth, A H, Williams, R C. Tubulin exchanges divalent cations at both guanine nucleotide-binding sites. J Biol Chem, 263(22), 10681-6, 1988.

Dammers, A.J., Levine, Y.K., Balasubramanian, K., and Beth, A.H. A planar rotor model for cholestane spin label motion in phospholipid multibilayers with high order. Chem. Phys., 127, 149-160, 1988.

Gettins, P, Beth, A H, Cunningham, L W. Proximity of thiol esters and bait region in human alpha 2-macroglobulin: paramagnetic mapping. Biochemistry, 27(8), 2905-11, 1988.

Cobb, C E, Beth, A H, Corbin, J D. Purification and characterization of an inactive form of cAMP-dependent protein kinase containing bound cAMP. J Biol Chem, 262(34), 16566-74, 1987.

Crews, B C, James, M W, Beth, A H, Gettins, P, Cunningham, L W. In support of the trap hypothesis. Chymotrypsin is not rigidly held in its complex with human alpha 2-macroglobulin. Biochemistry, 26(19), 5963-7, 1987.

Noland, T D, Abumrad, N A, Beth, A H, Garbers, D L. Protein phosphorylation in intact bovine epididymal spermatozoa: identification of the type II regulatory subunit of cyclic adenosine 3',5'-monophosphate-dependent protein kinase as an endogenous phosphoprotein. Biol Reprod, 37(1), 171-80, 1987.

Beth, A.H., Conturo, T.E., Venkataramu, S.D., and Staros, J.V. Dynamics and interactions of the anion channel in intact human erythrocytes: An EPR spectroscopic study employing a new membrane-impermeant bifunctional spin label. Biochemistry , 25, 3824-3832, 1986.

Beth, A.H., Robinson, B.H., Cobb, C.E., Dalton, L.R., Trommer, W.E., Birktoft, J., and Park, J.H. Interactions and spatial arrangement of spin labeled NAD+ bound to glyceraldehyde 3-phosphate dehydrogenase: Comparison of EPR and X-ray modeling data. J. Biol. Chem., 259, 9717-9728, 1984.

Beth, A.H., Balasubramanian, K., Robinson, B.H., Dalton, L.R., Venkataramu, S.D., and Park, J.H. Sensitivity of V2' saturation transfer electron paramagnetic resonance signals to anisotropic rotational diffusion with 15N spin labels: Effects of noncoincident magnetic and diffusion tensor principal axes. J. Phys. Chem, 87, 359-367, 1983.

Beth, A.H., Balasubramanian, K., Wilder, R.T., Venkataramu, S.D., Robinson, B.H., Dalton, L.R., Pearson, D.E., and Park, J.H. Structural and motional changes in glyceraldehyde 3-phosphate dehydrogenase upon binding to band 3 protein of the red blood cell membrane examined with [15N,2H] maleimide spin label and EPR. Proc. Natl. Acad. Sci. USA , 78, 4955-4959, 1981.

Beth, A.H., Venkataramu, S.D., Balasubramanian, K., Dalton, L.R., Robinson, B.H., Pearson, D.E., Park, C.R., and Park, J.H. 15N- and 2H-substituted maleimide spin labels: Improved sensitivity and resolution for Biological EPR studies. Proc. Natl. Acad. Sci. USA, 78, 967-971, 1981.

Beth, A.H., Perkins, R.C., Venkataramu, S.D., Pearson, D.E., Park, C.R., Park, J.H., and Dalton, L.R. Advantages of deuterium modification of nitroxide spin labels for biological EPR studies. Chem. Phys. Lett, 69, 24-18, 1980.


Postdoctoral Position Available
No

Postdoctoral Position Details
N/A

Updated Date
09/18/2009



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