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
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.
Hybrid NMR: A Union of Solution- and Solid-State NMR
Hybrid NMR (hdNMR) is a powerful new tool that combines the strengths of solution- and solid-state NMR to measure dipolar, chemical shift, and quadrupolar tensors in aqueous solution. We introduce the theory of hdNMR and partially randomly oriented (PRO) crystalline hydrogel samples. PRO samples produce randomly oriented spectra with characteristic Pake patterns from the solid state, yet they maintain the high-resolution dispersion of solution NMR experiments. With new pulse sequences, we show how hdNMR can be used to measure with high precision the 1Hα–13Cα dipolar tensor and carboxylate chemical shift anisotropy tensor of aspartate. These measurements contain detailed information on the distribution of electron density, interatomic distances, and the orientation dependence of molecular motion.
NSF CAREER Awarded to the Lorieau Group
The Lorieau group received the CAREER award from the National Science Foundation (NSF) for the project titled, “CAREER: Mechanism of Protein Catalyzed Membrane Fusion.” This project investigates the molecular mechanism of viral infection in the influenza virus and other related viral systems. News coverage on the grant can be found here. (Photo: UIC/Jenny Fontaine)
Membrane Fusion and Infection of the Influenza Hemagglutinin (Chapter)
The influenza virus is a major health concern associated with an estimated 5000 to 30,000 deaths every year (Reed et al. 2015) and a significant economic impact with the development of treatments, vaccinations and research (Molinari et al. 2007). The entirety of the influenza genome is comprised of only eleven coding genes. An enormous degree of variation in non-conserved regions leads to significant challenges in the development of inclusive inhibitors for treatment. The fusion peptide domain of the influenza A hemagglutinin (HA) is a promising candidate for treatment since it is one of the most highly conserved sequences in the influenza genome (Heiny et al. 2007), and it is vital to the viral life cycle. Hemagglutinin is a class I viral fusion protein that catalyzes the membrane fusion process during cellular entry and infection. Impediment of the hemagglutinin’s function, either through incomplete post-translational processing (Klenk et al. 1975; Lazarowitz and Choppin 1975) or through mutations (Cross et al. 2001), leads to non-infective virus particles. This review will investigate current research on the role of hemagglutinin in the virus life cycle, its structural biology and mechanism as well as the central role of the hemagglutinin fusion peptide (HAfp) to influenza membrane fusion and infection.