Arthur Johnson
Distinguished Professor
Regents Professor
Wehner - Welch Foundation Chair in Chemistry
Distinguished Professor of Molecular and Cellular Medicine
Professor of Biochemistry and Biophysics
Ph. D., University of Oregon
Contact
Information:
Department of Chemistry
Texas A&M University
College Station, TX 77843-3255
Phone:
(979) 862-3188
Fax: (979) 862-3339
ajohnson@medicine.tamhsc.edu
We are primarily investigating two different biochemical processes in my laboratory: the movement of proteins through or into a membrane (protein sorting), and the creation of holes in mammalian cell membranes by bacterial toxins. To understand how these processes are accomplished and regulated at the molecular level, we have employed a variety of biophysical, biochemical, and other techniques to examine the interactions and molecular architecture of free and membrane-bound macromolecular complexes, as well as changes in structure that are functionally important. We use fluorescence resonance energy transfer (FRET), photocrosslinking, or chemical crosslinking to determine the spatial arrangement of individual components within the complexes and to quantify the magnitude of conformational changes in the complexes. We also use various fluorescence techniques to detect and characterize the molecular interactions and conformational changes involved in the assembly, function, and regulation of the complexes, as well as to determine the structure of membrane-bound complexes. For example, our unique spectroscopic approach revealed that secretory proteins pass through the ER membrane via an aqueous, gated pore, not through the hydrophobic interior of the phospholipid bilayer, and that some, but not all, nascent protein chains fold far inside the ribosome to trigger interactions on the other side of the ER membrane. Many of these experiments utilize the chemically-modified aminoacyl-tRNA approach that we originated to incorporate non-natural amino acids into protein during translation.
Lin, P.-J., Jongsma, C. G., Pool, M. R., and Johnson, A. E. (2011) "Polytopic Membrane Protein Folding at L17 in the Ribosome Tunnel Initiates Cyclical Changes at the Translocon," J. Cell Biol. 195, 55-70.
Lin, P.-J., Jongsma, C. G., Liao, S., and Johnson, A. E. (2011) "Transmembrane Segments of Nascent Polytopic Membrane Proteins Control Cytosol/ER Targeting during Membrane Integration," J. Cell Biol. 195, 41-54.
Devaraneni, P., Conti, B., Matsumura, Y., Yang, Z., Johnson, A. E., and Skach, W. R.* (2011) "Stepwise Insertion and Inversion of a Type II Signal Anchor Occurs in the Ribosome-Sec61 Complex," Cell 146, 134-147.
Farrand, A. J., LaChapelle, S., Hotze, E., Johnson, A. E., and Tweten, R. K. (2010) "Only Two Amino Acids Are Essential for Cytolytic Toxin Recognition of Cholesterol at the Membrane Surface," Proc. Natl. Acad. Sci. (USA) 107, 4341-4346.
Saksena, S., Wahlman, J., Teis, D., Johnson, A. E., and Emr, S. D. (2009) "Functional Reconstitution of ESCRT-III Assembly and Disassembly," Cell 136, 97-109.
Lakkaraju, A. K. K., Mary, C., Scherrer, A., Johnson, A. E., and Strub, K. (2008) "SRP Maintains Nascent Chains Translocation-Competent by Slowing Translation Rates to Match Limiting Numbers of Targeting Sites," Cell 133, 440-451.
Alder, N. N., Jensen, R. E., and Johnson, A. E.* (2008) "Fluorescence Mapping of Mitochondrial TIM23 Complex Reveals a Water-Facing, Substrate-Interacting Helix Surface," Cell 134. 439-450.
Wahlman, J., DeMartino, G. N., Skach, W. R., Bulleid, N. J., Brodsky, J. L., and Johnson, A. E. (2007) "Real-time Fluorescence Detection of ERAD Substrate Retro-translocation in a Mammalian In Vitro System," Cell 129, 943-955.