Michael F Brown

Michael F Brown

Professor, Chemistry and Biochemistry-Sci
Professor, Applied Mathematics - GIDP
Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 621-2163

Research Interest

Michael F. Brown is Professor of Chemistry & Biochemistry at the University of Arizona. He is co-director of the Biological Physics Program and the Chemical Physics Program, and was a co-founder of the Biological Chemistry Program at the University of Arizona. He is internationally renowned for his work on the molecular basis of activation of G-protein-coupled receptors that are the targets for the majority of pharmaceuticals and medicines used by humans. The focus of his work is on biomembranes, with a particular emphasis on lipid-protein interactions in relation to potential drug targets involving membrane proteins. He is involved with investigation of the molecular basis of visual signaling involving rhodopsin. Moreover, Professor Brown is an expert in nuclear magnetic resonance (NMR) spectroscopy. His activities in the area of biomolecular NMR spectroscopy involve the devolvement and application of methods for studying the structure and dynamics of biomolecules. Michael Brown has authored over 130 original research papers, 10 book chapters, 4 book reviews, and has published more than 275 abstracts. His current H-index is 43. He numbers among his coworkers various prominent scientists worldwide. He presents his work frequently at national and international conferences, and is the recipient of a number of major awards. Professor Brown's many contributions have established him as a major voice in the area of biomembrane research and biomolecular spectroscopy. He is frequently a member of various review panels and exerts an influence on science policy at the national level. Among his accolades, he is an elected Fellow of the American Association for the Advancement of Science; American Physical Society; Japan Society for the Promotion of Science; and the Biophysical Society. He is a Fellow of the Galileo Circle of the University of Arizona. Most recently, he received the Avanti Award of the Biophysical Society. This premier honor recognizes his vast and innovative contributions to the field of membrane biophysics, and groundbreaking work in the development of NMR techniques to characterize lipid structure and dynamics. Most recently he presented the 2014 Avanti lecture of the Biophysical Society.

Publications

Shrestha, U. R., Perera, S. M., Bhowmik, D., Chawla, U., Mamontov, E., Brown, M. F., & Chu, X. (2016). Quasi-Elastic Neutron Scattering Reveals Ligand-Induced Protein Dynamics of a G-Protein–Coupled Receptor. Journal of Physical Chemistry Letters, 7, 4130−4136.
Mertz, B., Ritter, E., Bartl, F., & Brown, M. F. (2013). Lipid Bilayer Influences Rhodopsin Activation Probed by FTIR and UV-Visible Spectroscopy. Biophysical Journal, 104, 364.
Kinnun, J. J., Mallikarjunaiah, K. J., Petrache, H. I., & Brown, M. F. (2012). Intermembrane Forces Probed by Osmotic Stress and Solid-State 2H NMR Spectroscopy. Biophysical Journal, 102, 82.
Siminovitch, D. J., Brown, M. F., & Jeffrey, K. R. (1984). 14N NMR of lipid bilayers: Effects of ions and anesthetics. Biochemistry, 23(11), 2412-2420.

PMID: 6477874;Abstract:

The interaction of divalent and trivalent metal cations, ferricyanide, a lipophilic ion (tetraphenylborate), and a local anesthetic (tetracaine) with the phosphocholine head group of egg lecithin was investigated by using wide-line 14N and 31P NMR. Measurements of the 14N quadrupolar splittings in the presence of a variety of perturbing agents demonstrated that the 14N NMR technique can be used to directly monitor ion or anesthetic binding. The 14N quadrupolar splitting (ΔvQ) is a measure of the order parameter of the Cβ-N bond segment, and changes in ΔvQ as large as 3.5 kHz were observed. Moreover, a comparison of the changes in the quadrupolar splittings induced by the binding of ions or anesthetics provided a sensitive method of discriminating between these perturbing agents in their ability to alter the orientational order of the Cβ-N bond segment of the phosphocholine moiety. Without exception, addition of metal ions or anesthetics always resulted in a decrease of the 14N ΔvQ. This reduction reflects a change in the average orientation or degree of motional averaging at the Cβ-N bond segment position. In the case of metal ion binding, the strength of the interaction increased with the charge of the metal ion in the order Ca2+ Ln3+, in agreement with a previous 2H NMR study [Akutsu, H., & Seelig, J. (1981) Biochemistry 20, 7366-7373]. However, distinct differences were also noted between ions of the same charge, and in the case of the trivalent lanthanide ions, the 14N ΔvQ decreased in the sequence La3+ > Pr3+ > Eu3+ > Lu3+, following the order of the lanthanide contraction. The 14N and 31P line shapes in the presence of lanthanide ions showed that it is possible to clearly distinguish between the effects of paramagnetic (Pr3+, Eu3+, Dy3+, Tm3+) and diamagnetic (La3+, Lu3+) ions. Unusual, distinctive "asymmetric" 14N NMR line shapes were observed in the presence of the paramagnetic lanthanides, apparently due to incomplete averaging of the magnetic dipolar interaction between the bound lanthanide ion and the nitrogen nucleus. Addition of the lipophilic anion tetraphenylborate led to a slight reduction in the 14N ΔvQ, together with a dramatic decrease in the absolute value of the 31P chemical shielding anisotropy (Δσ). By contrast, the reduction of the 14N ΔvQ due to the presence of tetracaine was accompanied by a substantial increase in the 31P |Δσ|. In general, the measurements of the 14N ΔvQ as well as the 14N spin-lattice (T1) relaxation times support the notion that there is a rapid exchange of ions from the bulk medium to the ligand binding sites and among the various binding sites, in agreement with 2H NMR studies. The above results suggest that 14N NMR can provide a useful complement to 31P and 2H NMR techniques in studies of the influence of various perturbing agents on the orientational order and dynamics of the phosphocholine head groups in membranes. © 1984 American Chemical Society.

Moltke, S., Wallat, I., Sakai, N., Nakanishi, K., Brown, M. F., & Heyn, M. P. (1999). The angles between the C1-, C5-, and C9-methyl bonds of the retinylidene chromophore and the membrane normal increase in the M intermediate of bacteriorhodopsin: Direct determination with solid-state 2H NMR. Biochemistry, 38(36), 11762-11772.

PMID: 10512633;Abstract:

The orientations of three methyl bonds of the retinylidene chromophore of bacteriorhodopsin were investigated in the M photointermediate using deuterium solid-state NMR (2H NMR). In this key intermediate, the chromophore has a 13-cis, 15-anti conformation and a deprotonated Schiff base. Purple membranes containing wild-type or mutant D96A bacteriorhodopsin were regenerated with retinals specifically deuterated in the methyl groups of either carbon C1 or C5 of the β-ionone ring or carbon C9 of the polyene chain. Oriented hydrated films were formed by drying concentrated suspensions on glass plates at 86% relative humidity. The lifetime of the M state was increased in the wild-type samples by applying a guanidine hydrochloride solution at pH 9.5 and in the D96A sample by raising the pH. 2H NMR experiments were performed on the dark-adapted ground state (a 2:1 mixture of 13-cis, 15-syn and all-trans, 15-anti chromophores), the cryotrapped light-adapted state (all-trans, 15-anti), and the cryotrapped M intermediate (13-cis, 15-anti) at -50 °C. Bacteriorhodopsin was first completely converted to M under steady illumination of the hydrated films at +5 °C and then rapidly cooled to -50 °C in the dark. From a tilt series of the oriented sample in the magnetic field and an analysis of the 2H NMR line shapes, the angles between the individual C-CD3 bonds and the membrane normal could be determined even in the presence of a substantial degree of orientational disorder. While only minor differences were detected between dark- and light-adapted states, all three angles increase in the M state. This is consistent with an upward movement of the C5-C13 part of the polyene chain toward the cytoplasmic surface or with increased torsional strain. The C9-CD3 bond shows the largest orientational change of 7°in M. This reorientation of the chromophore in the binding pocket provides direct structural support for previous suggestions (based on spectroscopic evidence) for a steric interaction in M between the C9-methyl group and Trp 182 in helix F.