This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We are making a major effort to develop the utility of mass spectrometry to assist in the definition of integral membrane proteins and (especially ion channels) at atomic resolutions using diffraction methods. A number of publications have resulted from this work D.A. Doyle, J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, R. MacKinnon, """"""""The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity"""""""" Science 280, (1998) 69-77. R. MacKinnon, S.L. Cohen, A. Kuo, A. Lee, B.T. Chait """"""""Structural Conservation in Prokaryotic and Eukaryotic Potassium Channels"""""""" Science 280 (1998) 106-109. J.H. Morais Cabral, A. Lee, S. Cohen, B.T. Chait, M. Li, R. MacKinnon """"""""Structure of the HERG potassium channel amino-terminal domain: definition of a structural family of PAS domains"""""""" Cell 95 (1998) 649-655. J.M. Gulbis, M. Zhou, S. Mann, R. MacKinnon """"""""Structure of the Cytoplasmic ( Subunit-T1 Assembly of Voltage-Dependent K+ Channels"""""""" Science 289(2000) 123-127. M. Cadene, B.T. Chait """"""""A Robust Detergent-Friendly for Mass Spectrometric Analysis of Integral Membrane Proteins"""""""" Anal. Chem. 72 (2000) 5655-5658. S.L. Cohen, B.T. Chait """"""""Mass Spectrometry as a tool for Studying Protein Structure"""""""" Ann. Reviews of Biophysics and Biomolecular Structure 30 (2001) 67-85. R. Dutzler, ER Campbell, M. Cadene, B.T. Chait, R.MacKinnon """"""""X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity"""""""" Nature 415 (2002) 287-94. Y. Jiang, A. Lee, J. Chen, M. Cadene, B. T. Chait, R. MacKinnon """"""""Crystal structure and mechanism of a calcium-gated potassium channel"""""""" Nature 417 (2002) 515-522. Y. Jiang, A. Lee, J. Chen, M. Cadene, B. T. Chait, R. MacKinnon """"""""The open pore conformation of potassium channels"""""""" Nature 417 (2002) 523-526. Y. Jiang, A. Lee, J. Chen, V. Ruta, M. Cadene, B.T. Chait &Roderick MacKinnon """"""""X-ray structure of a voltage-dependent K+ channel"""""""" Nature 423 (2003) 33-41. The most recent work involves the Kir3.1 K(+) channel, which participates in heart rate control and neuronal excitability through G-protein and lipid signaling pathways. Expression in Escherichia coli has been achieved by replacing three fourths of the transmembrane pore with the pore of a prokaryotic Kir channel, leaving the cytoplasmic pore and membrane interfacial regions of Kir3.1 origin. Two structures were determined at 2.2 A. The selectivity filter is identical to the Streptomyces lividans K(+) channel within error of measurement (r.m.s.d.<0.2 A), suggesting that K(+) selectivity requires extreme conservation of three-dimensional structure. Multiple K(+) ions reside within the pore and help to explain voltage-dependent Mg(2+) and polyamine blockade and strong rectification. Two constrictions, at the inner helix bundle and at the apex of the cytoplasmic pore, may function as gates: in one structure the apex is open and in the other, it is closed. Gating of the apex is mediated by rigid-body movements of the cytoplasmic pore subunits. Phosphatidylinositol 4,5-biphosphate-interacting residues suggest a possible mechanism by which the signaling lipid regulates the cytoplasmic pore.
| Manning, Lois R; Popowicz, Anthony M; Padovan, Julio C et al. (2017) Gel filtration of dilute human embryonic hemoglobins reveals basis for their increased oxygen binding. Anal Biochem 519:38-41 |
| Boice, Michael; Salloum, Darin; Mourcin, Frederic et al. (2016) Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells. Cell 167:405-418.e13 |
| Chait, Brian T; Cadene, Martine; Olinares, Paul Dominic et al. (2016) Revealing Higher Order Protein Structure Using Mass Spectrometry. J Am Soc Mass Spectrom 27:952-65 |
| Krutchinsky, Andrew N; Padovan, Júlio C; Cohen, Herbert et al. (2015) Maximizing ion transmission from atmospheric pressure into the vacuum of mass spectrometers with a novel electrospray interface. J Am Soc Mass Spectrom 26:649-58 |
| Mast, Fred D; Rachubinski, Richard A; Aitchison, John D (2015) Signaling dynamics and peroxisomes. Curr Opin Cell Biol 35:131-6 |
| Krutchinsky, Andrew N; Padovan, Júlio C; Cohen, Herbert et al. (2015) Optimizing electrospray interfaces using slowly diverging conical duct (ConDuct) electrodes. J Am Soc Mass Spectrom 26:659-67 |
| Oricchio, Elisa; Papapetrou, Eirini P; Lafaille, Fabien et al. (2014) A cell engineering strategy to enhance the safety of stem cell therapies. Cell Rep 8:1677-1685 |
| Zhong, Yu; Morris, Deanna H; Jin, Lin et al. (2014) Nrbf2 protein suppresses autophagy by modulating Atg14L protein-containing Beclin 1-Vps34 complex architecture and reducing intracellular phosphatidylinositol-3 phosphate levels. J Biol Chem 289:26021-37 |
| Indiani, Chiara; O'Donnell, Mike (2013) A proposal: Source of single strand DNA that elicits the SOS response. Front Biosci (Landmark Ed) 18:312-23 |
| Di Virgilio, Michela; Callen, Elsa; Yamane, Arito et al. (2013) Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science 339:711-5 |
Showing the most recent 10 out of 67 publications
