Department of Chemistry
University of Illinois at Chicago
Chicago IL 60607
Research in the Lorieau group integrates Biophysics, Physical Chemistry, Structural Biology and Biochemistry in elucidating the interplay between biomolecular structure, dynamics, chemistry and function.
With a combination of solution- and solid-state Nuclear Magnetic Resonance spectroscopies, computational tools and other biophysical methods, our research focuses on membrane protein structure and dynamics, membrane protein biochemistry, the development of theory and techniques to enhance the precision and resolution of structural and dynamic information by NMR, and the investigation of molecular dynamics as it relates to enzymatic catalysis and kinetics.
Membranes and Membrane Proteins
High-Resolution NMR Methods Development
Partial alignment, residual dipolar couplings and molecular symmetry in solution NMR
Residual dipolar couplings (RDCs) and residual anisotropic chemical shifts (RACSs) are produced by the partial alignment of solution NMR samples. RDCs and RACSs yield high-resolution structural and dynamic information on the orientation of bonds and chemical groups in molecules. Many molecules form oligomers or have intrinsic symmetries, which may simplify the analysis of their partial alignment datasets. In this report, we explore the theory of partial alignment using an irreducible spherical representation, and we investigate the impact of molecular symmetry on the alignment of molecules. Though previous studies have reported simplified relationships on the partial alignment of molecules bearing different symmetry groups, we show that these simplified relationships may not be universal and only apply to a limited set of systems.
Super resolution NOESY spectra of proteins
Spectral resolution remains one of the most significant limitations in the NMR study of biomolecules. We present the srNOESY (super resolution nuclear Overhauser effect spectroscopy) experiment, which enhances the resolution of NOESY cross-peaks at the expense of the diagonal peak line-width. We studied two proteins, ubiquitin and the influenza hemagglutinin fusion peptide in bicelles, and we achieved average resolution enhancements of 21–47% and individual peak enhancements as large as ca. 450%. New peaks were observed over the conventional NOESY experiment in both proteins as a result of these improvements, and the final structures generated from the calculated restraints matched published models. We discuss the impact of the experimental parameters, spin diffusion and the information content of the srNOESY lineshape.
The Lorieau Group (2018)
Picture of Justin L Lorieau, Zoe Petros, Charles DeLisle, Indrani Banerjee, Alec Malooley, H. Bhagya Mendis and Medine Ayhan
Congratulations to Dr. Adrian Draney
Congratulations to Adrian Draney on earning his PhD! Dr. Draney is the second member of the Lorieau group to receive his PhD. He will join the laboratory of Prof. Guido Pintacuda at the Ecole normale supérieure de Lyon to conduct solid-state NMR experiments.
New Members Zoe Petros and Alec Malooley
Welcome to Zoe Petros and Alec Malooley, the newest graduate student members of the Lorieau group. Zoe joins us from the University of Illinois, Urbana-Champaign and Alec comes from the University of Illinois, Chicago. They will be working on membrane protein structures by NMR.
Congratulations to Dr. Sean Smrt
Congratulations to Sean Smrt on earning his PhD! Dr. Smrt is the first member of the Lorieau group to receive his PhD. He will join the laboratory of Prof. Tim Cross at the National High Magnetic Field Laboratory at Florida State University to conduct solid-state NMR experiments on the membrane proteins of Mycobacterium tuberculosis.
Mollib: a molecular and NMR data analysis software
Mollib is a software framework for the analysis of molecular structures, properties and data with an emphasis on data collected by NMR. It uses an open source model and a plugin framework to promote community-driven development of new and enhanced features. Mollib includes tools for the automatic retrieval and caching of protein databank (PDB) structures, the hydrogenation of biomolecules, the analysis of backbone dihedral angles and hydrogen bonds, and the fitting of residual dipolar coupling (RDC) and residual anisotropic chemical shift (RACS) data. In this article, we release version 1.0 of mollib and demonstrate its application to common molecular and NMR data analyses.
Structure and Dynamics of Membrane Proteins and Membrane Associated Proteins with Native Bicelles from Eukaryotic Tissues
In vitro studies of protein structure, function and dynamics typically preclude the complex range of molecular interactions found in living tissues. In vivo studies elucidate these complex relationships, yet they are typically incompatible with the extensive and controlled biophysical experiments available in vitro. We present an alternative approach by extracting membranes from eukaryotic tissues to produce native bicelles to capture the rich and complex molecular environment of in vivo studies while retaining the advantages of in vitro experiments. Native bicelles derived from chicken egg or mouse cerebrum tissues contain a rich composition of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidic acid (PA), lysolipids, cholesterol, ceramides (CM) and sphingomyelin (SM). The bicelles also contain source-specific lipids such as triacylglycerides (TAGs) and sulfatides from egg and brain tissues, respectively. With the influenza hemagglutinin fusion peptide (HAfp) and the C-terminal Src Homology domain of Lymphocyte-specific protein-tyrosine kinase (lck-cSH2), we show that membrane proteins and membrane associated proteins reconstituted in native bicelles produce high-resolution NMR data and probe native protein-lipid interactions.