PhD

Professor Emerita

Biochemistry

Education

BS	Zoology	Colorado State University	Fort Collins, Colo.
PhD	Molecular Biology	University of Wisconsin	Madison, Wis.

Research Areas

Molecular chaperones in protein export; analysis of protein-protein interactions.

Research Description

We aim to elucidate the mechanism of protein export in Escherichia coli with emphasis on the interactions of the protein components of the pathway. Translocation of specific, newly synthesized polypeptides across biological membranes is a ubiquitous process that is essential for living cells. Whether the process occurs in eukaryotes or in prokaryotes in almost all cases molecular chaperones are involved. Chaperones are a family of proteins that display the remarkable ability to recognize and bind polypeptides based on the fact that the ligands are in a nonnative state.

Our research is focused on the molecular chaperone SecB and its promiscuous interactions with polypeptide ligands as well as its specific interactions with the protein SecA, which is an ATPase that serves as the motor for transfer of proteins across the membrane. We study the interactions among the proteins using a wide range of techniques. These include the following biophysical techniques: column chromatography, dynamic light scattering, calorimetry, fluorescence spectroscopy, analytical centrifugation, mass spectrometry, and electron paramagnetic spin resonance. We also have established an in vitro protein translocation system and assays of the ATPase activity of SecA.

Honors and Service

• Member, National Academy of Sciences
• Member, American Academy of Arts and Sciences
• Fellow, American Academy of Microbiology
• Fellow, American Association for the Advancement of Science
• Executive Council: Protein Society (1996-99)
• MERIT Award NIH (1993-03)
• Conference Organization
  • Chair Gordon Conference on Bacterial Cell Surface, 1988
  • Co-organizer 14th Symposium of the Protein Society, 2000
• Eli Lilly Award in Microbiology or Immunology, 1984
• Editorial Boards
  • Journal of Bacteriology (1982-1997)
  • Protein Science (1992-1996)

Selected Publications

Sanganna Gari RR, Chattrakun K, Marsh BP, Mao C, Chada N, Randall LL, King GM. (Sci ). Direct visualization of the E. coli Sec translocase engaging precursor proteins in lipid bilayers. 2019 Jun 12;5(6):eaav9404. doi: 10.1126/sciadv.aav9404. eCollection 2019 Jun. [PubMed]

Bariya P, Randall LL. (2018). Coassembly of SecYEG and SecA Fully Restores the Properties of the Native Translocon. J Bacteriol. 201(1). doi: 10.1128/JB.00493-18. Print 2019 Jan 1. [PubMed]

Findik BT, Smith VF, Randall LL. (2018). Penetration into membrane of amino-terminal region of SecA when associated with SecYEG in active complexes. Protein Sci. 27(3):681-691. doi: 10.1002/pro.3362. [PubMed]

Findik BT, Randall LL. (2017). Determination of the intracellular concentration of the export chaperone SecB in Escherichia coli. PLoS One. 12(8):e0183231. doi: 10.1371/journal.pone.0183231. [PubMed]

Chada N, Sigdel KP, Gari RR, Matin TR, Randall LL, King GM. (2015). Glass is a Viable Substrate for Precision Force Microscopy of Membrane Proteins. Sci Rep. 5:12550. doi: 10.1038/srep12550. [PubMed]

Suo Y, Hardy SJS, Randall LL. (2015). The basis of asymmetry in the SecA:SecB complex. J Mol Biol. 427(4):887-900. doi: 10.1016/j.jmb.2014.12.008. [PubMed]

Mao C, Cheadle CE, Hardy SJ, Lilly AA, Suo Y, Sanganna Gari RR, King GM, Randall LL. (2013). Stoichiometry of SecYEG in the active translocase of Escherichia coli varies with precursor species. Proc Natl Acad Sci U S A. 110(29):11815-20. doi: 10.1073/pnas.1303289110. [PubMed]

Sanganna Gari RR, Frey NC, Mao C, Randall LL, King GM. (2013). Dynamic structure of the translocon SecYEG in membrane: direct single molecule observations. J Biol Chem. 288(23):16848-54. doi: 10.1074/jbc.M113.471870. [PubMed]

Suo Y, Hardy SJ, Randall LL. (2011). Orientation of SecA and SecB in complex, derived from disulfide cross-linking. J Bacteriol. 193(1):190-6. doi: 10.1128/JB.00975-10. [PubMed]

Randall LL, Henzl MT. (2010). Direct identification of the site of binding on the chaperone SecB for the amino terminus of the translocon motor SecA. Protein Sci. 19(6):1173-9. doi: 10.1002/pro.392. [PubMed]

Crane JM, Lilly AA, Randall LL. (2010). Characterization of interactions between proteins using site-directed spin labeling and electron paramagnetic resonance spectroscopy. Methods Mol Biol. 619:173-90. doi: 10.1007/978-1-60327-412-8_11. [PubMed]

Lilly AA, Crane JM, Randall LL. (2009). Export chaperone SecB uses one surface of interaction for diverse unfolded polypeptide ligands. Protein Sci. 18(9):1860-8. doi: 10.1002/pro.197. [PubMed]

Current Funding

• NIH R01 to 2020 (41 years of continuous NIH funding since 1980)