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.
Conformation transitions of the polypeptide-binding pocket support an active substrate release from Hsp70s. Yang J, Zong Y, Su J, Li H, Zhu H, Columbus L, Zhou L, Liu Q. Conformation transitions of the polypeptide-binding pocket support an active substrate release from Hsp70s. Nat Commun. 2017 Oct 31;8(1):1201. doi: 10.1038/s41467-017-01310-z. PubMed PMID: 29084938; PubMed Central PMCID: PMC5662698.
Modulating Vascular Hemodynamics With an Alpha Globin Mimetic Peptide (HbαX).Keller TC 4th, Butcher JT, Broseghini-Filho GB, Marziano C, DeLalio LJ, Rogers S, Ning B, Martin JN, Chechova S, Cabot M, Shu X, Best AK, Good ME, Simão Padilha A, Purdy M, Yeager M, Peirce SM, Hu S, Doctor A, Barrett E, Le TH, Columbus L, Isakson BE. Hypertension. 2016 Dec;68(6):1494-1503. Epub 2016 Oct 31.
Opa+ Neisseria gonorrhoeae has reduced survival in human neutrophils via Src family kinase-mediated bacterial trafficking into mature phagolysosomes. Johnson MB, Ball LM, Daily KP, Martin JN, Columbus L, and Criss AK. Cellular Microbiology. 17:648 – 665 (2015).
Tuning micelle dimensions and properties with binary surfactant mixtures. OliverRC, Lipfert, Fox DA, LoRH, KimJJ, DoniachS, Columbus L. Langmuir. 30:13353 – 13361 (2014).
Mapping membrane protein dynamics: a comparison of site-directed spin labeling to NMR 15N-relaxation measurements. Lo RH, Kroncke BM, Solomon T, Columbus L. Biophysical Journal.107:1697 – 1702 (2014).
Structure of the Neisserial Outer Membrane Protein Opa60: Loop Flexibility Essential to Receptor Recognition and Bacterial Engulfment. Fox DA, Larsson P, Lo RH, Kroncke BM, Kasson PM, Columbus L. J Am Chem Soc. 136:9938-9946 (2014).