Bob Sauer's Lab

KARL SCHMITZ

Karl Schmitz
Postdoc Associate (2010 -June 2015) and
Postdoc Fellow (July 2015-June 2017)
The Medical Foundation

Faculty
University of Delaware
schmitzk [at] udel.edu

Alvaro, A.J., Schmitz, K.R., Sello, J.K., Baker, T.A. & Sauer, R.T. (2016) Highly dynamic interactions maintain kinetic stability of the ClpXP protease during the ATP-fueled mechanical cycle. ACS Chem. Biol. 30 March 2016.

Schmitz, K.R. and Sauer, R.T. (2014) Substrate delivery by the AAA+ ClpX and ClpC1 unfoldases activates the mycobacterial ClpP1P2 peptidase Mol. Microbiology 93(4):617-28. doi: 10.1111/mmi.12694. Epub 2014 Jul 13.

Carney, D., Schmitz, K.R., Truong, J., Sauer, R.T., and Sello, J.K. (2014) Restriction of the conformational dynamics of the cyclic acyldepsipeptide macrocycle improves antibacterial activity by enhancing both ClpP peptidase binding and activation. J. Amer. Chem. Soc. 136, 1922-1929.

Carney, D.W., Compton, C.L., Schmitz, K.R., Stevens, J.P., Sauer, R.T. & Jason K. Sello (2014) A simple fragment of the acyldepsipeptide antibacterial agents is necessary and sufficient for ClpP activation and antibacterial activity. Chembiochem. 15(15):2216-20. doi: 10.1111/mmi.12694. Epub 2014 Jul 13.

Stinson, B.M., Nager, A.R., Glynn, S.E., Schmitz, K.R., Baker, T.A. & Sauer, R.T. (2013) Nucleotide Binding and Conformational Switching in the Hexameric Ring of a AAA+ Machine. Cell 153(3): 628-39.

ALVARO "AJ" AMOR

Alvaro "AJ" Amor
Graduate Student (June 2013-July 2017)

alamor [at] mit.edu

Alvaro, A.J., Schmitz, K.R., Sello, J.K., Baker, T.A. & Sauer, R.T. (2016) Highly dynamic interactions maintain kinetic stability of the ClpXP protease during the ATP-fueled mechanical cycle. ACS Chem. Biol. 30 March 2016.

OHAD YOSEFSON

Ohad Yosefson
Postdoctoral Associate (October 2011 - May 2017)

ohady [at] mit.edu

Iosefson, O., Olivares, A.O., Baker, T.A. & Sauer, R.T. (2015) Dissection of Axial-Pore Loop Function during Unfolding and Translocation by a AAA+ Proteolytic Machine. Cell Reports 11; 12(6), 1032-41. doi: 10.1016/j.celrep.2015.07.007.

Iosefson, O., Nager, A.R., Baker, T.A. & Sauer, R.T. (2015) Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine Nat. Chem. Biol. 11(3):201-6. doi: 10.1038/nchembio.1732.

Olivares, A.O., Nager, A.R., Iosefson, O., Sauer, R.T. & Baker, T.A. (2014) Mechanochemical basis of protein degradation by a double-ring AAA+ machine Nat. Struct. Mol. Biol. 21, 871-875.

REUBEN SAUNDERS

Reuben Saunders
UROP (February 2014-June 2016)
Summer Research Assistant
(June 2016 - September 2016)

MPhil, Medical Science (CIMR)
Churchill Scholar
University of Cambridge, Churchill College

VLADIMIR BAYTSHTOK

Vladimir Baytshtok
Graduate Student (June 2011 - August 2016)

Postdoctoral Associate
Memorial Sloan Kettering Cancer Center
Christopher Lima Lab
baytshtv [at] mskcc.org

Baytshtok, V., Baker, T.A. & Sauer, R.T. (2015) Assaying the kinetics of protein denaturation catalyzed by AAA+ unfolding machines and proteases. Proc. Natl. Acad. Sci. USA 112, 5377-5382. pubmed. citation

ADRIAN OLIVARES

Adrian Olivares
Research Scientist (July 2015-August 2016)

Faculty
Vanderbilt University
adrian.olivares [at] vanderbilt.edu

Olivares, A.O., Baker, T.A., and Sauer, R.T. (2016) Mechanistic insights into bacterial AAA+ proteases and protein-remodeling machines. Nat. Rev. Microbiol 14(1):33-44.

Iosefson, O., Olivares, A.O., Baker, T.A., and Sauer, R.T. (2015) Dissection of axial-pore loop function during unfolding and translocation by a AAA+ proteolytic machine. Cell Reports 12(6):1032-1041, PMC4536184.

Olivares, A.O., Nager, A.R., Iosefson, O., Sauer, R.T., and Baker, T.A. (2014) Mechanochemical basis of protein degradation by a double-ring AAA+ machine. Nat. Struct. Mol. Biol. 21(10):871-875, PMC4190165.

Cordova, J.C.*, Olivares, A.O.*, Shin, Y.*, Stinson, B.M., Calmat, S., Schmitz, K.R., Aubin-Tam, M.E., Baker, T.A., Lang, M.J., and Sauer, R.T. (2014) Stochastic but highly coordinated protein unfolding and polypeptide translocation by the ClpXP proteolytic machine. Cell 158(3):647-658, PMC4134808. *equal contribution

Aubin-Tam, M.E.*, Olivares, A.O.*, Sauer, R.T., Baker, T.A., and Lang, M.J. (2011) Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine. Cell 145(2):257-267, PMC3108460. *equal contribution

JONATHAN D. GRABENSTATTER

Jon Grabenstatter
Graduate Student (August 2012 - August 2015)

Barthelme, D., Chen, J.Z., Grabenstatter, J., Baker, T.A., and Sauer, R.T. (2014) Architecture and assembly of the archaeal Cdc48•20S proteasome. Proc. Natl. Acad. Sci. USA 111, E1687-1694.

BENJAMIN STINSON

Ben Stinson
Graduate Student (June 2010 - February 2015)
and Poitras Pre-doctoral Fellow
(September 2013-August 2014)
Visiting Scientist through March 2015

Postdoctoral Fellow
Harvard Medical School

benjamin_stinson [at] hms.harvard.edu

Stinson, B.M., Baytshtok, V., Schmitz, K.R., Baker, T.A. & Sauer, R.T. (2015) Subunit asymmetry and roles of conformational switching in the hexameric AAA+ ring of ClpX. Nat. Struct. Mol. Biol. 22, 411–416.

Cordova, J.C, Olivares, A.O., Shin, Y., Stinson, B.M., Calmat, S., Schmitz, K.R., Aubin-Tam, M-E. Baker, T.A., Lang, M.J., and Sauer R.T. (2014) Stochastic but highly coordinated protein unfolding and translocation by the ClpXP proteolytic machine. Cell 158(3): 647-58. doi: 10.1016/j.cell.2014.05.043.

Stinson, B.M., Nager, A.R., Glynn, S.E., Schmitz, K.R., Baker, T.A. & Sauer, R.T. (2013) Nucleotide Binding and Conformational Switching in the Hexameric Ring of a AAA+ Machine. Cell 153(3): 628-39.

DOMINIK BARTHELME

Dominik Barthelme
Postdoctoral Associate
January 2011-March 2013 and April 2014-Feb. 2015
German Research Foundation Fellow
April 2013 - March 2014

Scientist, Biochemistry
Neon Therapeutics, Inc.
Cambridge, Massachusetts
dbarthelme [at] neontherapeutics.com

Barthelme, D., Jauregui, R. & Sauer, R.T. (2015) An ALS disease mutation in Cdc48/p97 impairs 20S proteasome binding and proteolytic communication. Protein Sci. (in press).

Barthelme, D., Chen, J.Z., Grabenstatter, J., Baker, T.A., and Sauer, R.T. (2014) Architecture and assembly of the archaeal Cdc48•20S proteasome. Proc. Natl. Acad. Sci. USA 111, E1687-1694.

Barthelme, D. & Sauer, R.T. (2013) Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase. Proc. Natl. Acad. Sci. USA 110(9): 3327-32.

Barthelme, D. & Sauer, R.T. (2012) Identification of the Cdc48•20S proteasome as an ancient AAA+ proteolytic machine. Science 2012 Aug 17;337(6096):843-6. Epub 2012 July 26. PMID 22837385.

ANNA DE REGT

Anna de Regt

Microbiology Graduate Student (June 2010 - September 2014)
Visiting Scientist (October 1, 2014-January 2015)

Fred Hutchinson Cancer Research Center
aderegt [at] fredhutch.org

de Regt, A.K., Baker, T.A., & Sauer, R.T. (2015) Steric clashes with bound OMP peptides activate the DegS stress-response protease. Proc. Natl. Acad. Sci. USA 112, 3326-3331.

de Regt, A.K., Kim, S., Sohn, J., Grant, R.A., Baker, T.A., & Sauer, R.T. (2015) A conserved activation cluster is required for allosteric communication in HtrA-family proteases. Structure 23, 517-526.

de Regt, A.K., Yin, Y., Withers, T.R., Wang, X., Baker, T.A., Sauer, R.T., and Yu, H.D. (2014) Overexpression of CupB5 activates alginate overproduction in Pseudomonas aeruginosa by a novel AlgW-dependent mechanism. Mol. Micro. 93, 415-425.

JASON SELLO

Jason Sello
Martin Luther King, Jr. Visiting Associate Professor (September 2013 - July 2014)

Faculty
Brown University
Department of Chemistry
jason_sello [at] brown.edu

Carney, D.W., Compton, C.L., Schmitz, K.R., Stevens, J.P., Sauer, R.T. & Jason K. Sello (2014) A simple fragment of the acyldepsipeptide antibacterial agents is necessary and sufficient for ClpP activation and antibacterial activity. Chembiochem. (in press).

Carney, D., Schmitz, K.R., Truong, J., Sauer, R.T., and Sello, J.K. (2014) Restriction of the conformational dynamics of the cyclic acyldepsipeptide macrocycle improves antibacterial activity by enhancing both ClpP peptidase binding and activation. J. Amer. Chem. Soc. 136, 1922-1929.

SEOKHEE KIM

Seok Hee Kim

Postdoc Associate (2008 - June 2012) and Postdoctoral Fellow (July 2012-January 2014)
The Medical Foundation
Faculty
Seoul National University
Department of Chemistry
seokheekim [at] snu.ac.kr

Kim S, Sauer RT. (2014) Distinct regulatory mechanisms balance DegP proteolysis to maintain cellular fitness during heat stress. Genes Dev. 2014 Apr 15;28(8):902-11. doi: 10.1101/gad.238394.114. PMID: 24736846

Kim, S. & Sauer, R.T. (2012) Cage assembly of DegP protease is not required for substrate-dependent regulation of Proteolytic activity or high-temperature cell survival. Proc. Natl. Acad. Sci. USA 109(19):7263-7268. Epub 2012 April 23. PMID 22529381 [Indexed for MEDLINE] PMCID: PMC3358883.

Kim, S., Grant, R.A. & Sauer, R. T. (2011) Covalent linkage of distinct substrate degrons controls assembly and disassembly of DegP proteolytic cages.Cell. 2011 Apr 1;145(1):67-78. PubMed PMID: 21458668; PubMed Central PMCID: PMC3075617.

MATTHEW WOHLEVER

Matthew L. Wohlever

National Science Foundation
Graduate Research Fellow (2009-2012) and
Graduate Student (June 2009 - May 2013)
Visiting Scientist through July 2013

Faculty
The University of Toledo
Department of Chemistry and Biochemistry
matthew.wohlever[at] toledo.edu

Gora, K.G., Cantin, A., Wohlever, M., Joshi, K.K., Perchuk, B.S., Chien, P., Laub, M.T. (2013) Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus. Mol Microbiol Mar; 87(6) 1277-89, PMID 23368090.

Hesse, W.R., Steiner, M., Wohlever, M.L., Kamm, R.D., Hwang, W., and Lang, M.J. (2013) Modular aspects of kinesin force generation machinery. Biophys J. PMID 23663840.

Vieux, E.F., Wohlever, M.L., Chen, J.Z., Sauer, R.T. & Baker, T.A. (2013) Distinct quaternary structures of the AAA+ Lon protease control substrate degradation. Proc. Natl. Acad. Sci. USA.

Wohlever ML, Nager AR, Baker TA . & Sauer, RT (2013) Engineering fluorescent protein substrates for the AAA+ Lon Protease . Protein Eng Des Sei - Epub 2013. January 28. PMID 23359718.

ANDREW R. "DREW" NAGER

Andrew R. Nager
Graduate Student (2009-2012)
Visiting Scientist through February 2013

Pfizer
andrew.nager[at] pfizer.com

Stinson, B.M., Nager, A.R., Glynn, S.E., Schmitz, K.R., Baker, T.A. & Sauer, R.T. (2013) Nucleotide Binding and Conformational Switching in the Hexameric Ring of a AAA+ Machine. Cell 153(3): 628-39.

Wohlever ML, Nager AR, Baker TA . & Sauer, RT (2013) Engineering fluorescent protein substrates for the AAA+ Lon Protease . Protein Eng Des Sei - Epub 2013. January 28. PMID 23359718.

Glynn, S.E., Nager, A.R. Baker, T.A. & Sauer, R.T. (2012) Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine. Nat. Struct. Mol. Biol. 19, 616-622.

Nager, A.R., Baker, T.A. & Sauer, R.T. (2011) Stepwise unfolding of a β-barrel protein by the AAA+ ClpXP protease. J. Mol. Biol. 413, 4-16 .

Glynn, S.E., Martin, A., Nager, A.R., Baker, T.A. and Sauer R.T. (2009) Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine. Cell, 139, 744-756.

RANDALL MAULDIN

Randall Mauldin
Posdoctoral Associate (March 2010-June 2011)
and NIH Postdoctoral Fellow (July 2011- March 2012)
Email (rmauldin [at] alumni.unc.edu)

Scientist II
Biogen Idec

Mauldin, R.V., and Sauer R.T. (2013) Allosteric regulation of DegS protease subunits through a shared energy landscape. Nature Chemical Biology , 9, 90-96.

STEVEN GLYNN

Steven Glynn
Postdoc Associate (2005-January 2012)

Faculty
Stony Brook University
steven.glynn [at] stonybrook.edu

Stinson, B.M., Nager, A.R., Glynn, S.E., Schmitz, K.R., Baker, T.A. & Sauer, R.T. (2013) Nucleotide Binding and Conformational Switching in the Hexameric Ring of a AAA+ Machine. Cell 153(3): 628-39.

Glynn, S.E., Nager, A.R., Baker, T.A. & Sauer, R.T. (2012) Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine. Nat. Struct. Mol. Biol. 19, 616-622.

Glynn, S.E., Martin, A., Nager, A.R., Baker, T.A. and Sauer R.T. (2009) Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine. Cell, 139, 744-756.

SANTIAGO LIMA

Santiago Lima
Postdoc Associate (2008-2010)
NIH Postdoc Fellow (July 2010-December 2011)

Postdoctoral Fellow
Department of Chemistry and Molecular Biology
Virginia Commonwealth University
Richmond, Virginia
santiago.lima [at] vcuhealth.org

Lima, S., Guo, M.S., Chaba, R., Gross, C.A. & Sauer, R.T. (2013) Dual Molecular Signals Mediate the Bacterial Response to Outer-Membrane Stress. Science 340(6134):837-41.

JIEJIN CHEN

Jiejin Chen
Postdoc Associate (2009-November 2011)
Email (jiejinc [at] gmail.com)

Scientist II
Takeda Pharmaceuticals, Inc.

SHANKAR SUNDAR

Shankar Sundar
Graduate Student (2006-2011)
Email (ssundar06 [at] gmail.com)

Consultant
Blue Matter Consulting

Sundar, S., Baker, T.A. & Sauer, R.T. (2012) The I domain of the AAA+ Hs1UV protease coordinates substrate binding, ATP hydrolysis, and protein degradation. Protein Science 21, 188-198.

Sundar, S., McGinness, K.E., Baker, T.A. & Sauer, R.T. (2010) Multiple sequence signals direct recognition and degradation of protein substrates by the AAA+ protease Hs1UV. J. Mol. Biol. 403, 420-429.

JUNGSAN SOHN

Jungsan "J" Sohn
NIH Postdoc Fellow (2008-2011)

Faculty
Johns Hopkins University School of Medicine
jsohn [at] jhmi.edu

Sohn J., Grant, R.A., Sauer, R.T. (2010) Allostery is an intrinsic property of the protease domain of DegS: Implications for enzyme function and evolution J. Biol. Chem. 285: 34039-47

Sohn J., Grant, R.A., Sauer, R.T. (2009) OMP peptides activate the DegS protease by a relief of inhibition mechanism. Structure 17, 1411-21

Sohn, J. & Sauer, R.T. (2009) OMP peptides modulate the activity of Degs protease by differential binding to active and inactive conformations. Mol. Cell 33, 64-74.

Sohn, J., Grant, R.A., Sauer, R.T. (2007) Allosteric activation of DegS, a stress sensor PDZ-protease. Cell. 131 572-583.