Linda ColumbusLinda Columbus

  • Assistant Professor of Chemistry

 

  • B.A., Smith College, 1996
  • Ph.D., University of California, Los Angeles, 2001
  • NIH Postdoctoral Fellow, The Scripps Research Institute, 2002 - 2007

  • Mead Honored Faculty, 2008
  • Jeffress Memorial Trust, 2007

Biophysical Chemistry: Membrane protein structure, function, and dynamics

Membrane proteins facilitate the transfer of information across lipid bilayers, comprise approximately 25% of a typical proteome, and represent over half of all drug targets. The membrane proteins that mediate interactions between bacterial pathogens and hosts are of particular interest to our laboratory. Invasive bacterial pathogens are responsible for many lethal diseases and epidemics, including plague and meningitis. Although these bacteria have diverse mechanisms of cellular invasion, all of the pathways rely upon interactions between host and bacterial membrane proteins.

Our lab seeks to determine the structure and conformational changes of membrane proteins involved in bacterial infection using a combination of site-directed spin labeling (SDSL), nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography, and also to develop tools to accelerate membrane protein structure determination by these methods.

Representative Publications

McCleverty C*, Columbus L*, Kreusch A, Lesley SA. The X-ray crystal structure of the soluble domain of the membrane protein TM1634: A novel fold. Protein Science 17: 869-877 (2008)

Lipfert J, Columbus L, Chu V, Lesley SA, Doniach S. Size and shape of detergent micelles determined by small-angle X-ray scattering. Journal of Physical Chemistry B 111: 12427-12438 (2007)

Lipfert J, Columbus L, Chu V, Doniach S. Analysis of small-angle X-ray scattering data of protein-detergent complexes with singular value decomposition.Journal of Applied Crystallography 40: S235-S239 (2007)

Columbus L, Lipfert J, Klock H, Millet I, Doniach S, Lesley SA. Expression, purification, and characterization of Thermotoga maritima membrane proteins for structure determination. Protein Science 15: 961-975 (2006)

Columbus L, Peti W, Herrmann T, Etezady T, Wüthrich K. NMR structure determination of the conserved hypothetical protein TM1816 from Thermotoga maritima. Proteins: Structure, Function and Bioinformatics 60: 552-557 (2005)

Liang ZC, Lou Y, Freed JH, Columbus L, Hubbell WL. A multifrequency electron spin resonance study of T4 lysozyme dynamics using the slowly relaxing local structure model. Journal of Physical Chemistry B 108: 17649-17659 (2004)

Columbus L, Hubbell WL. Mapping backbone dynamics in solution with site-directed spin labeling: GCN4-58 bZip free and bound to DNA. Biochemistry 43: 7273-7287 (2004)

Columbus L, Hubbell WL. A new spin on protein dynamics. Trends in Biochemical Sciences, 27: 288-295 (2002)

Columbus L, Kalai T, Jeko J, Hideg K, Hubbell WL. Molecular motion of spin labeled side chains in a-helices: Analysis by variation of side chain structure. Biochemistry 40: 3828-3846 (2001)

Gaponenko V, Howarth JW, Columbus L, Gasmi-Seabrook G, Yuan J, Hubbell WL, Rosevear PR. Protein global fold determination using site-directed spin and isotope labeling. Protein Science 9: 302-309 (2000)

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 38: 10324-10335 (1999)