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.

Membranes and Membrane Proteins

Membrane proteins represent approximately a third of expressed proteins in cells, yet they are under-represented in structural databases. We use solution and solid-state NMR to characterize the structures and dynamics of membrane proteins, and the curvature and fusion of membranes.

Viral Infection Proteins and Mechanisms

Influenza, HIV and Ebola viruses have an outer membrane envelope that must fuse with the host cell membrane on cellular entry. We use NMR to characterize the structures and mechanism of viral fusion proteins and the role of membrane curvature.

High-Resolution NMR Methods Development

Solution and solid-state NMR report detailed information on the distribution of electrons, the distances between atoms and the dynamics of molecules at the atomic level. We investigate new methods to increase the resolution of NMR structures, molecular dynamics and the distribution of conformation ensembles.
Publication March 06, 2020

Pro‐islet Amyloid Polypeptide in Micelles Contains a Helical Prohormone Segment

Citation: DeLisle CF, Malooley AL, Banerjee I, Lorieau JL. (2020) Pro‐islet Amyloid Polypeptide in Micelles Contains a Helical Prohormone Segment. FEBS. J. : . doi: 10.1111/febs.15253.

Pro‐islet amyloid polypeptide (proIAPP) is the prohormone precursor molecule to IAPP, also known as amylin. IAPP is a calcitonin family peptide hormone that is cosecreted with insulin, and largely responsible for hunger satiation and metabolic homeostasis. Amyloid plaques containing mixtures of mature IAPP and misprocessed proIAPP deposit on, and destroy pancreatic β‐cell membranes, and they are recognized as a clinical hallmark of type 2 diabetes mellitus. In order to better understand the interaction with cellular membranes, we solved the solution NMR structure of proIAPP bound to dodecylphosphocholine micelles at pH 4.5. We show that proIAPP is a dynamic molecule with four α‐helices. The first two helices are contained within the mature IAPP sequence, while the second two helices are part of the C‐terminal prohormone segment (Cpro). We mapped the membrane topology of the amphipathic helices by paramagnetic relaxation enhancement, and we used CD and diffusion‐ordered spectroscopy to identify environmental factors that impact proIAPP membrane affinity. We discuss how our structural results relate to prohormone processing based on the varied pH environments and lipid compositions of organelle membranes within the regulated secretory pathway, and the likelihood of Cpro survival for cosecretion with IAPP.

Publication August 12, 2019

Partial alignment, residual dipolar couplings and molecular symmetry in solution NMR

Citation: Lorieau JL. (2019) Partial alignment, residual dipolar couplings and molecular symmetry in solution NMR. J. Biomol. NMR. 73: 477-491. doi: 10.1007/s10858-019-00256-2.

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.

Publication April 30, 2019

Super resolution NOESY spectra of proteins

Citation: DeLisle CF, Mendis HB, Lorieau JL. (2019) Super resolution NOESY spectra of proteins. J. Biomol. NMR. 73(3-4): 105-116. doi: 10.1007/s10858-019-00231-x.

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.

News September 01, 2018

The Lorieau Group (2018)

group photo Picture of Justin L Lorieau, Zoe Petros, Charles DeLisle, Indrani Banerjee, Alec Malooley, H. Bhagya Mendis and Medine Ayhan

News December 07, 2017

Congratulations to Dr. Adrian Draney

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.

News November 16, 2017

New Members Zoe Petros and Alec Malooley

Zoe Petros 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.

News November 04, 2017

Congratulations to Dr. Sean Smrt

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.

Publication October 15, 2017

Mollib: a molecular and NMR data analysis software

Citation: Lorieau JL. (2017) Mollib: a molecular and NMR data analysis software. J. Biomol. NMR. 69(2): 69-80. doi: 10.1007/s10858-017-0142-5.

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.