Linda Columbus

Education

  • BA, Smith College
  • PhD, University of California Los Angeles

Primary Appointment

  • Assistant Professor, Chemistry

Contact

Research Interest(s)

Biophysical Chemistry: Membrane protein structure, function, and dynamics

Research Description

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 dynamics of membrane proteins involved in bacterial pathogenesis and to develop tools to accelerate membrane protein structure determination using a combination of site-directed spin labeling (SDSL), nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography.

Selected Publications

  • Butcher J, Johnson T, Beers J, Columbus L, Isakson B. Hemoglobin α in the blood vessel wall. Free radical biology & medicine. 2014;73 136-142. PMID: 24832680
  • Fox D, Larsson P, Lo R, Kroncke B, Kasson P, Columbus L. Structure of the neisserial outer membrane protein opa60: loop flexibility essential to receptor recognition and bacterial engulfment. Journal of the American Chemical Society. 2014;136(28): 9938-46. PMID: 24813921 | PMCID: PMC4105060
  • Kenwood B, Weaver J, Bajwa A, Poon I, Byrne F, Murrow B, Calderone J, Huang L, Divakaruni A, Tomsig J, Okabe K, Lo R, Cameron Coleman G, Columbus L, Yan Z, Saucerman J, Smith J, Holmes J, Lynch K, Ravichandran K, Uchiyama S, Santos W, Rogers G, Okusa M, Bayliss D, Hoehn K. Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane. Molecular metabolism. 2014;3(2): 114-23. PMID: 24634817 | PMCID: PMC3953706
  • Straub A, Butcher J, Billaud M, Mutchler S, Artamonov M, Nguyen A, Johnson T, Best A, Miller M, Palmer L, Columbus L, Somlyo A, Le T, Isakson B. Hemoglobin α/eNOS Coupling at Myoendothelial Junctions Is Required for Nitric Oxide Scavenging During Vasoconstriction. Arteriosclerosis, thrombosis, and vascular biology. 2014. PMID: 25278292
  • Anton B, Chang Y, Brown P, Choi H, Faller L, Guleria J, Hu Z, Klitgord N, Levy-Moonshine A, Maksad A, Mazumdar V, McGettrick M, Osmani L, Pokrzywa R, Rachlin J, Swaminathan R, Allen B, Housman G, Monahan C, Rochussen K, Tao K, Bhagwat A, Brenner S, Columbus L, de Crécy-Lagard V, Ferguson D, Fomenkov A, Gadda G, Morgan R, Osterman A, Rodionov D, Rodionova I, Rudd K, Söll D, Spain J, Xu S, Bateman A, Blumenthal R, Bollinger J, Chang W, Ferrer M, Friedberg I, Galperin M, Gobeill J, Haft D, Hunt J, Karp P, Klimke W, Krebs C, Macelis D, Madupu R, Martin M, Miller J, O'Donovan C, Palsson B, Ruch P, Setterdahl A, Sutton G, Tate J, Yakunin A, Tchigvintsev D, Plata G, Hu J, Greiner R, Horn D, Sjölander K, Salzberg S, Vitkup D, Letovsky S, Segrè D, DeLisi C, Roberts R, Steffen M, Kasif S. The COMBREX project: design, methodology, and initial results. PLoS biology. 2013;11(8): e1001638. PMID: 24013487 | PMCID: PMC3754883
  • Fox D, Columbus L. Solution NMR resonance assignment strategies for β-barrel membrane proteins. Protein science : a publication of the Protein Society. 2013;22(8): 1133-40. PMID: 23754333 | PMCID: PMC3832050
  • Li J, Liu Q, Xiao L, Haverstick D, Dewald A, Columbus L, Kelly K, Landers J. Label-free method for cell counting in crude biological samples via paramagnetic bead aggregation. Analytical chemistry. 2013;85(23): 11233-9. PMID: 24187938
  • Oliver R, Lipfert J, Fox D, Lo R, Doniach S, Columbus L. Dependence of micelle size and shape on detergent alkyl chain length and head group. PloS one. 2013;8(5): e62488. PMID: 23667481 | PMCID: PMC3648574
  • Elkin S, Kumar A, Price C, Columbus L. A broad specificity nucleoside kinase from Thermoplasma acidophilum. Proteins. 2012;81(4): 568-82. PMID: 23161756 | PMCID: PMC3595323
  • Johnstone S, Kroncke B, Straub A, Best A, Dunn C, Mitchell L, Peskova Y, Nakamoto R, Koval M, Lo C, Lampe P, Columbus L, Isakson B. MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth muscle cell proliferation. Circulation research. 2012;111(2): 201-11. PMID: 22652908 | PMCID: PMC3405546
  • Kroncke B, Columbus L. Backbone (1)H, (13)C and (15)N resonance assignments of the α-helical membrane protein TM0026 from Thermotoga maritima. Biomolecular NMR assignments. 2012. PMID: 23011877 | PMCID: NIHMS410416
  • Kroncke B, Columbus L. Identification and removal of nitroxide spin label contaminant: impact on PRE studies of α-helical membrane proteins in detergent. Protein science : a publication of the Protein Society. 2012;21(4): 589-95. PMID: 22389096 | PMCID: PMC3375759
  • Straub A, Lohman A, Billaud M, Johnstone S, Dwyer S, Lee M, Bortz P, Best A, Columbus L, Gaston B, Isakson B. Endothelial cell expression of haemoglobin α regulates nitric oxide signalling. Nature. 2012;491(7424): 473-7. PMID: 23123858 | PMCID: PMC3531883
  • Dewald A, Hodges J, Columbus L. Physical determinants of β-barrel membrane protein folding in lipid vesicles. Biophysical journal. 2011;100(9): 2131-40. PMID: 21539780 | PMCID: PMC3149260
  • Beuck C, Szymczyna B, Kerkow D, Carmel A, Columbus L, Stanfield R, Williamson J. Structure of the GLD-1 homodimerization domain: insights into STAR protein-mediated translational regulation. Structure (London, England : 1993). 2010;18(3): 377-89. PMID: 20223220 | PMCID: PMC2837851
  • Kroncke B, Horanyi P, Columbus L. Structural origins of nitroxide side chain dynamics on membrane protein α-helical sites. Biochemistry. 2010;49(47): 10045-60. PMID: 20964375 | PMCID: PMC2991438
  • Columbus L, Lipfert J, Jambunathan K, Fox D, Sim A, Doniach S, Lesley S. Mixing and matching detergents for membrane protein NMR structure determination. Journal of the American Chemical Society. 2009;131(21): 7320-6. PMID: 19425578 | PMCID: PMC2751809
  • McCleverty C, Columbus L, Kreusch A, Lesley S. Structure and ligand binding of the soluble domain of a Thermotoga maritima membrane protein of unknown function TM1634. Protein science : a publication of the Protein Society. 2008;17(5): 869-77. PMID: 18369189 | PMCID: PMC2327271
  • Lipfert J, Columbus L, Chu V, Lesley S, Doniach S. Size and shape of detergent micelles determined by small-angle X-ray scattering. The journal of physical chemistry. B. 2007;111(43): 12427-38. PMID: 17924686
  • Columbus L, Lipfert J, Klock H, Millett I, Doniach S, Lesley S. Expression, purification, and characterization of Thermotoga maritima membrane proteins for structure determination. Protein science : a publication of the Protein Society. 2006;15(5): 961-75. PMID: 16597824 | PMCID: PMC2242514
  • Columbus L, Peti W, Etezady-Esfarjani T, Herrmann T, Wüthrich K. NMR structure determination of the conserved hypothetical protein TM1816 from Thermotoga maritima. Proteins. 2005;60(3): 552-7. PMID: 15937903
  • Columbus L, Hubbell W. Mapping backbone dynamics in solution with site-directed spin labeling: GCN4-58 bZip free and bound to DNA. Biochemistry. 2004;43(23): 7273-87. PMID: 15182173
  • Columbus L, Hubbell W. A new spin on protein dynamics. Trends in biochemical sciences. 2002;27(6): 288-95. PMID: 12069788
  • Gaponenko V, Howarth J, Columbus L, Gasmi-Seabrook G, Yuan J, Hubbell W, Rosevear P. Protein global fold determination using site-directed spin and isotope labeling. Protein science : a publication of the Protein Society. 2000;9(2): 302-9. PMID: 10716182 | PMCID: PMC2144541