Linda Columbus


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

Primary Appointment

  • Associate Professor, Chemistry


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

  • Post-expression strategies for structural investigations of membrane proteins. Current opinion in structural biology. 2015;32 131-138. PMID: 25951412
  • Columbus L, Kroncke B. Solution NMR Structure Determination of Polytopic α-Helical Membrane Proteins: A Guide to Spin Label Paramagnetic Relaxation Enhancement Restraints. Methods in enzymology. 2015;557 329-48. PMID: 25950972
  • Gray C, Price C, Lee C, Dewald A, Cline M, McAnany C, Columbus L, Mura C. Known structure, unknown function: An inquiry-based undergraduate biochemistry laboratory course. Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology. 2015. PMID: 26148241
  • 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
  • Johnson M, Ball L, Daily K, Martin J, Columbus L, Criss A. Opa+ Neisseria gonorrhoeae exhibits reduced survival in human neutrophils via Src family kinase-mediated bacterial trafficking into mature phagolysosomes. Cellular microbiology. 2014. PMID: 25346239 | PMCID: PMC4402142
  • 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
  • Lo R, Kroncke B, Solomon T, Columbus L. Mapping membrane protein backbone dynamics: a comparison of site-directed spin labeling with NMR 15N-relaxation measurements. Biophysical journal. 2014;107(7): 1697-702. PMID: 25296323 | PMCID: PMC4190660
  • Oliver R, Lipfert J, Fox D, Lo R, Kim J, Doniach S, Columbus L. Tuning micelle dimensions and properties with binary surfactant mixtures. Langmuir : the ACS journal of surfaces and colloids. 2014;30(44): 13353-61. PMID: 25312254
  • 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
  • Columbus L, Kálai T, Jekö 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(13): 3828-46. PMID: 11300763
  • 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
  • Gross A, Columbus L, Hideg K, Altenbach C, Hubbell W. 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. PMID: 10441126