Publications
http://www.ncbi.nlm.nih.gov/myncbi/collections/bibliography/48138435/
Witten J*, Ruschak A, Poterba T*, Jaramillo A*, Miranker AD, Jaswal SS. Mapping protein conformational landscapes under strongly native conditions with hydrogen exchange mass spectrometry. Journal of Physical Chemistry B DOI: 10.1021/acs.jpcb.5b04528 Publication Date (Web): July 6, 201510.1021/acs.jpcb.5b04528 (2015)
Cohen P*, Dill K, Jaswal SS. Modeling the solvation of nonpolar amino acids in guanidinium chloride solutions. Journal of Physical Chemistry B 118, 10618–10623 (2014)
Wagaman A, Coburn A, Brand-Thomas I*, Dash B*, Jaswal SS. A comprehensive database of verified experimental data on protein folding kinetics. Protein Science 23, 1808–1812 (2014)
Wagaman A, Jaswal SS. Capturing protein folding-relevant topology via absolute contact order variants. Journal of Theoretical and Computational Chemistry 13, 14005-14031 (2014)
Shamsuddin R*, Doktorova M*, Jaswal SS, Lee-St.John A and McMenimen K. Computational Prediction of Hinge Axes in Proteins, BMC Bioinformatics 15:S2. (2013)
Jaswal SS, O’Hara PB, Williamson P, Springer A. Teaching structure: Student use of software tools for understanding macromolecular structure in an undergraduate biochemistry course. Biochemistry and Molecular Biology Education, 41, 351–359 (2013)
Jaswal SS. Biological Insights from Hydrogen Exchange Mass Spectrometry. Biochim Biophys Acta Proteins and Proteomics, 1834, 1188-1201 (2013) published online October 29, 2012
Jaswal SS. Alpha-lytic protease. Handbook of Proteolytic Enzymes, 3rd edition. Elsevier Press, edited by Neil D. Rawlings and Guy Salvesen 2358–2365 (2012)
Jaswal SS, Miranker AD. Scope and Utility of Hydrogen Exchange as a Tool for Mapping Landscapes. Protein Science, 16, 2378-90 (2007)
Jaswal SS, Truhlar SE, Dill KA, Agard DA. Comprehensive analysis of protein folding activation thermodynamics reveals a universal behavior violated by kinetically stable proteases. Journal of Molecular Biology 347, 355-66 (2005)
Jaswal SS, Sohl JL, Davis JD, Agard DA. Energetic landscape of alpha-lytic protease optimizes longevity through kinetic stability. Nature 415, 343-436 (2002)
Cunningham EL, Jaswal SS, Sohl JL, Agard DA. Kinetic stability as a mechanism for protease longevity. Proceedings of the National Academy of Sciences 96, 11008-11014 (1999)
Sohl JL#, Jaswal SS#, Agard DA. Unfolded conformations of a-lytic protease are more stable than its native state. Nature 395, 817-819 (1998)
#These authors contributed equally to this work
Mink S, Jaswal SS, Burk O, Klempnauer K. The v-Myb oncoprotein activates C/EBP beta expression by stimulating an autoregulatory loop at the C//EBP beta promoter. Biochim Biophys Acta Gene Structure and Expression 1447, 175-184 (1999)
McVay LD, Jaswal SS, Kennedy C, Hayday A, Carding SR. The generation of human gammadelta T cell repertoires during fetal development. Journal of Immunology 160, 5851-60 (1998)
Witten J*, Ruschak A, Poterba T*, Jaramillo A*, Miranker AD, Jaswal SS. Mapping protein conformational landscapes under strongly native conditions with hydrogen exchange mass spectrometry. Journal of Physical Chemistry B DOI: 10.1021/acs.jpcb.5b04528 Publication Date (Web): July 6, 201510.1021/acs.jpcb.5b04528 (2015)
Cohen P*, Dill K, Jaswal SS. Modeling the solvation of nonpolar amino acids in guanidinium chloride solutions. Journal of Physical Chemistry B 118, 10618–10623 (2014)
Wagaman A, Coburn A, Brand-Thomas I*, Dash B*, Jaswal SS. A comprehensive database of verified experimental data on protein folding kinetics. Protein Science 23, 1808–1812 (2014)
Wagaman A, Jaswal SS. Capturing protein folding-relevant topology via absolute contact order variants. Journal of Theoretical and Computational Chemistry 13, 14005-14031 (2014)
Shamsuddin R*, Doktorova M*, Jaswal SS, Lee-St.John A and McMenimen K. Computational Prediction of Hinge Axes in Proteins, BMC Bioinformatics 15:S2. (2013)
Jaswal SS, O’Hara PB, Williamson P, Springer A. Teaching structure: Student use of software tools for understanding macromolecular structure in an undergraduate biochemistry course. Biochemistry and Molecular Biology Education, 41, 351–359 (2013)
Jaswal SS. Biological Insights from Hydrogen Exchange Mass Spectrometry. Biochim Biophys Acta Proteins and Proteomics, 1834, 1188-1201 (2013) published online October 29, 2012
Jaswal SS. Alpha-lytic protease. Handbook of Proteolytic Enzymes, 3rd edition. Elsevier Press, edited by Neil D. Rawlings and Guy Salvesen 2358–2365 (2012)
Jaswal SS, Miranker AD. Scope and Utility of Hydrogen Exchange as a Tool for Mapping Landscapes. Protein Science, 16, 2378-90 (2007)
Jaswal SS, Truhlar SE, Dill KA, Agard DA. Comprehensive analysis of protein folding activation thermodynamics reveals a universal behavior violated by kinetically stable proteases. Journal of Molecular Biology 347, 355-66 (2005)
Jaswal SS, Sohl JL, Davis JD, Agard DA. Energetic landscape of alpha-lytic protease optimizes longevity through kinetic stability. Nature 415, 343-436 (2002)
Cunningham EL, Jaswal SS, Sohl JL, Agard DA. Kinetic stability as a mechanism for protease longevity. Proceedings of the National Academy of Sciences 96, 11008-11014 (1999)
Sohl JL#, Jaswal SS#, Agard DA. Unfolded conformations of a-lytic protease are more stable than its native state. Nature 395, 817-819 (1998)
#These authors contributed equally to this work
Mink S, Jaswal SS, Burk O, Klempnauer K. The v-Myb oncoprotein activates C/EBP beta expression by stimulating an autoregulatory loop at the C//EBP beta promoter. Biochim Biophys Acta Gene Structure and Expression 1447, 175-184 (1999)
McVay LD, Jaswal SS, Kennedy C, Hayday A, Carding SR. The generation of human gammadelta T cell repertoires during fetal development. Journal of Immunology 160, 5851-60 (1998)
CV
Research
Proteins are the molecules that carry out the vast majority of the jobs necessary to keep cells functioning, including breaking down and synthesizing nutrients, carrying messages and cargo, providing structural support, and raising the alarm and defending against attack. The code by which sets of three nucleotides in DNA specify the 20 chemical building blocks known as amino acids that comprise the alphabet of proteins was deciphered long ago. With the explosion of genome sequencing, the order in which amino acids need to be strung together to make each and every protein that is found in nearly 200 different organisms, including human, is now known. There is tremendous potential within this wealth of sequence information to contribute to better understanding of biology and to improve medicine by pinpointing differences in proteins from different samples – for example between healthy and tumor cells. However this contribution is currently limited because protein chemists have yet to solve the 2nd half of the genetic code that truly links protein sequence to biological function.
The missing link arises because proteins function not as linear chains of amino acids, but rather each protein folds into a specific compact three-dimensional structure, whose shape is the key to its ability to carry out its particular tasks. Cracking the code for this molecular origami– how an amino acid sequence specifies the correctly folded structure, the pathway for reaching it, and the ability to remain stable and folded – is the fundamental puzzle that has captivated protein chemists for decades. Because some proteins spontaneously find their way back to the same folded structure after being unfolded in the test-tube, investigators have found clues into the folding process by “interrogating” proteins through heating or adding chemicals to the protein sample, and watching them unfold, then refold when returned to less harsh conditions. While the harsh conditions of traditional folding methods yield insight into folding for model proteins that are “well-behaved” and resilient to being harassed by heat and chemicals, most proteins do not recover and little information about their folding is gained through such treatment.
Our lab studies protein folding using an array of biophysical, biochemical, and computational approaches. We focus on “folding-challenged” proteins that are very different from most model proteins studied. These rogue proteins are characterized by an extremely high energy barrier that prevents the folded structure from unfolding, which may be a feature common to proteins involved in diseases such as Alzheimer’s and Parkinson’s as well. We are also developing a milder technique to probe folding that exploits mass spectrometry to expand the range of proteins accessible to folding investigations. Since protein misfolding has been linked to an ever-increasing number of diseases – including neurodegeneration, aging, cancer, and HIV infection – over the past two decades, the ability to explore the full diversity of mechanisms for coupling protein folding to biological function will be crucial for understanding the pathology of these diseases as well as for developing novel design strategies for therapeutic and engineering purposes.
The missing link arises because proteins function not as linear chains of amino acids, but rather each protein folds into a specific compact three-dimensional structure, whose shape is the key to its ability to carry out its particular tasks. Cracking the code for this molecular origami– how an amino acid sequence specifies the correctly folded structure, the pathway for reaching it, and the ability to remain stable and folded – is the fundamental puzzle that has captivated protein chemists for decades. Because some proteins spontaneously find their way back to the same folded structure after being unfolded in the test-tube, investigators have found clues into the folding process by “interrogating” proteins through heating or adding chemicals to the protein sample, and watching them unfold, then refold when returned to less harsh conditions. While the harsh conditions of traditional folding methods yield insight into folding for model proteins that are “well-behaved” and resilient to being harassed by heat and chemicals, most proteins do not recover and little information about their folding is gained through such treatment.
Our lab studies protein folding using an array of biophysical, biochemical, and computational approaches. We focus on “folding-challenged” proteins that are very different from most model proteins studied. These rogue proteins are characterized by an extremely high energy barrier that prevents the folded structure from unfolding, which may be a feature common to proteins involved in diseases such as Alzheimer’s and Parkinson’s as well. We are also developing a milder technique to probe folding that exploits mass spectrometry to expand the range of proteins accessible to folding investigations. Since protein misfolding has been linked to an ever-increasing number of diseases – including neurodegeneration, aging, cancer, and HIV infection – over the past two decades, the ability to explore the full diversity of mechanisms for coupling protein folding to biological function will be crucial for understanding the pathology of these diseases as well as for developing novel design strategies for therapeutic and engineering purposes.
