Department of Chemistry
University of Illinois at Chicago
Chicago IL 60607

Research Overview

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. HAfp Structure

  • Membrane protein and membrane channel structure, dynamics and function
  • Methods for the high-resolution characterization of structure and dynamics for solution-state and solid-state nuclear magnetic resonace of large molecular-weight biomolecules
  • Software development for the simulation of magnetic resonance, including data and statistical analysis of multidimensional datasets

Recent Publications and Group News

News: NSF CAREER Awarded to the Lorieau Group

group photo 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)

Publication: Membrane Fusion and Infection of the Influenza Hemagglutinin (Chapter)

Citation: Smrt ST, Lorieau JL. (2016) Membrane Fusion and Infection of the Influenza Hemagglutinin (Chapter). Adv. Exp. Med. Biol. (Springer): 1-18. doi: 10.1007/5584_2016_174.

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.

News: The Lorieau Group (2016)

group photo Group photo of the Lorieau Group. Members, from left to right, are ustin L Lorieau, Adrian W Draney, Alec Malooney, Charles D DeLisle, Indrani Banerjee, Ed Gluzman, Bhagya Mendis and Sean T Smrt.

News: Chemistry Demo Day

Demo day demonstration 1 Chemistry demo day with Adrian W Draney, Charles Delisle and Sean T Smrt.

Publication: A Positively Charged Liquid Crystalline Medium for Measuring Residual Dipolar Couplings in Membrane Proteins by NMR

Citation: Thiagarajan-Rosenkranz P, Draney AW, Smrt ST, Lorieau JL. (2015) A Positively Charged Liquid Crystalline Medium for Measuring Residual Dipolar Couplings in Membrane Proteins by NMR. J. Am. Chem. Soc. 137(37): 11932-11934. doi: 10.1021/jacs.5b07515.

jacs toc Residual Dipolar Couplings (RDCs) are integral to the refinement of membrane protein structures by NMR since they accurately define the orientation of helices and other structural units. Only a small set of liquid crystals used for RDC measurements are compatible with the detergents needed in membrane protein studies. The available detergent-compatible liquid crystals are negatively charged, thus offering effectively only one of five orthogonal components of the alignment Saupe matrix. In this communication, we present a robust liquid crystalline medium that is positively charged, pinacyanol acetate (PNA), for the determination of orthogonal sets of RDCs in membrane proteins. This new medium promises to enhance the accuracy of membrane protein structures and the measurement of dynamics based on RDCs.Residual Dipolar Couplings (RDCs) are integral to the refinement of membrane protein structures by NMR since they accurately define the orientation of helices and other structural units. Only a small set of liquid crystals used for RDC measurements are compatible with the detergents needed in membrane protein studies.The available detergent-compatible liquid crystals are negatively charged, thus offering effectively only one of five orthogonal components of the alignment Saupe matrix. In this communication, we present a robust liquid crystalline medium that is positively charged, pinacyanol acetate (PNA), for the determination of orthogonal sets of RDCs in membrane proteins. This new medium promises to enhance the accuracy of membrane protein structures and the measurement of dynamics based on RDCs.

Publication: The Influenza Hemagglutinin Fusion Domain is an Amphipathic Helical-Hairpin that Functions by Inducing Membrane Curvature

Citation: Smrt ST, Draney AW, Lorieau JL. (2015) The Influenza Hemagglutinin Fusion Domain is an Amphipathic Helical-Hairpin that Functions by Inducing Membrane Curvature. J. Biol. Chem. 290: 228-238. doi: 10.1074/jbc.M114.611657.

jacs toc The highly conserved N-terminal 23 residues of the hemagglutinin glycoprotein, known as the fusion peptide domain (HAfp23), is vital to the membrane fusion and infection mechanism of the influenza virus. HAfp23 has a helical hairpin structure consisting of two tightly packed amphiphilic helices that rest on the membrane surface. We demonstrate that HAfp23 is a new class of amphipathic helix that functions by leveraging the negative curvature induced by two tightly packed helices on membranes. The helical hairpin structure has an inverted wedge shape characteristic of negative curvature lipids, with a bulky hydrophobic region and a relatively small hydrophilic head region. The F3G mutation reduces this inverted wedge shape by reducing the volume of its hydrophobic base. We show that despite maintaining identical backbone structures and dynamics as the wild type HAfp23, the F3G mutant has an attenuated fusion activity that is correlated to its reduced ability to induce negative membrane curvature. The inverted wedge shape of HAfp23 is likely to play a crucial role in the initial stages of membrane fusion by stabilizing negative curvature in the fusion stalk.